This site is intended for US healthcare professionals
This site is intended for US healthcare professionals
The information contained in this site is intended for US healthcare professionals only
Astellas does not own the website you will be visiting and is not responsible for the content or services contained on that website. This link is provided as a convenience to the users of this site.
Go to VYLOYaccess.com to complete the online Patient Enrollment Form. You can also enroll your patient via fax by downloading the Patient Enrollment Form and faxing a completed form to 1-855-272-6653.
Patient Connect offers additional patient and caregiver support to patients who have been prescribed VYLOY. This program helps connect your patient and their caregivers to educational resources and support to help them manage daily life while on treatment. When a patient or caregiver calls VYLOY Support Solutions, a trained representative will assess their specific needs and customize a search of various independent local and national organizations§ that may provide the support and resources requested,|| such as:
1-855-272-6609 • Monday-Friday, 8:00 AM-8:00 PM ET VYLOYSupportSolutions.com
*Subject to eligibility. Program terms and conditions apply. Void where prohibited by law.
†By enrolling in the VYLOY Copay Assistance Program ("Program"), the patient acknowledges that they currently meet the eligibility criteria and will comply with the following terms and conditions: The Program is for eligible patients with commercial prescription insurance for VYLOY® (zolbetuximab-clzb) and is good for use only with a valid prescription for VYLOY. The Program has an annual maximum copay assistance limit of $25,000, with the annual period starting on the date of Program card activation. After the annual maximum on copay assistance is reached, patient will be responsible for the remaining monthly out-of-pocket costs for VYLOY. The Program is not valid for patients whose prescription claims are reimbursed, in whole or in part, by any state or federal government program, including, but not limited to, Medicaid, Medicare, Medigap, Department of Defense (DoD), Veterans Affairs (VA), TRICARE, Puerto Rico Government Insurance, or any state patient or pharmaceutical assistance program. Patients who move from commercial insurance to federal or state prescription health insurance will no longer be eligible, and agree to notify the Program of any such change. This offer is not valid for cash paying patients. Patients agree not to seek reimbursement from any health insurance or third party for all or any part of the benefit received by the patient through the Program. This offer is not conditioned on any past, present, or future purchase of VYLOY. This offer is not transferable, has no cash value, and cannot be combined with any other offer, free trial, prescription savings card, or discount (including any program offered by a third-party payer or pharmacy benefits manager, or an agent of either, that adjusts patient cost-sharing obligations, through arrangements that may be referred to as "accumulator" or "maximizer" programs). The full value of the Program benefits is intended to pass entirely to the eligible patient. The benefit available under this Program is valid only for the patient's out-of-pocket medication costs for VYLOY. The benefit is not valid for any other out-of-pocket costs such as medication administration charges or other healthcare provider services. No other individual or entity (including, without limitation, third-party payers, pharmacy benefit managers, or the agents of either) is entitled to receive any benefit, discount, or other amount in connection with this Program. This offer is not health insurance and is only valid for patients in the 50 United States, Washington DC, and Puerto Rico. This Program is void where prohibited by law. No membership fees. Certain rules and restrictions apply. Astellas reserves the right to revoke, rescind, or amend this offer without notice for any reason (including to ensure that the offer is utilized solely for the patient's benefit).
‡Information and materials provided by VYLOY Support Solutions are to assist providers, but the responsibility to determine coverage, reimbursement, and appropriate coding for a particular patient and/or procedure remains at all times with the provider.
§Support is provided through third-party organizations that operate independently and are not controlled or endorsed by Astellas.
||Availability of support and eligibility requirements are determined by these organizations.
To request these and other resources for your office, you can also connect with an Astellas representative.
TRANSCRIPT
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze, and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs, including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough, and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Please see Important Safety Information continued in this video and full Prescribing Information at VYLOYhcp.com.
NURSE 1: As long as I’ve been an oncology nurse, it still gets to me every time I see a patient for their first cancer treatment infusion. The worry on their face breaks my heart.
NURSE 2: I feel the same. They don’t know what to expect, or how they’ll feel. It’s a lot of unknowns.
NURSE 1: But you know what? When I’ve done my homework, I can help my patients be better prepared for infusion day.
NURSE 2: I know, there are several VYLOY resources that have helped me learn what to expect and how to support my patients.
NURSE 1: You know what works for me? I took those resources and came up with an infusion-day check list to help keep me organized.
NURSE 2: How’s that work?
NURSE 1: First I start with the technical things I need to do as far as the infusion goes—like checking the IV line.
NURSE 1: I always make sure I’m using the recommended in-line filter and that I do not co-administer other drugs through the same infusion line as VYLOY.
NURSE 2: But what about patients who have central ports?
NURSE 1: From what I’ve read, no incompatibilities have been observed with closed system transfer devices or central ports with certain materials. The Prescribing Information has the full details.
NURSE 2: That’s really helpful to know.
NURSE 2: So what’s next on your checklist?
NURSE 1: I double check the prepared infusion bag and note the time. The prepared infusion bag can be kept at room temperature, 15 to 30 degrees Celsius or 59 to 86 degrees Fahrenheit, for no longer than 6 hours, from the end of the preparation of the infusion bag to the completion of the infusion. Once I’m done, I start with my patient checklist.
NURSE 2: I bet I know where that starts...
BOTH: Premedication
NURSE 1: Absolutely. These patients can be pretty sick, so I always ask how they’re feeling, especially if it’s their first infusion.
NURSE 1: If they tell me they’re nauseated or they’ve been vomiting, I make sure their symptoms are reduced to Grade 1 or less before we start the first infusion.
VYLOY is emetogenic. In clinical trials, the median time to onset of nausea and/or vomiting was within the first hour after starting the VYLOY infusion. It’s important that patients are premedicated with a combination of antiemetics like NK-1 and/or 5-HT3 receptor blockers, as well as other drugs as indicated, for the prevention of nausea and vomiting. Keep in mind that there are no contraindications for VYLOY. I always let my patients know in advance that they can expect premedication with every VYLOY infusion.
NURSE 2: I think that’s a big reassurance for the patient...to know that we’re doing everything we can to help them.
NURSE 1: Exactly...and if they do experience Grade 2 or 3 nausea or vomiting, I’ll stop the infusion until the symptoms are resolved to Grade 1 or less. Then I resume the infusion at a reduced infusion rate for the remaining infusion. If the patient experiences Grade 4 vomiting, I need to immediately stop the infusion and permanently discontinue VYLOY.
NURSE 1: The prescribing information shows the infusion rates for first and subsequent infusions. I like to use this information to help patients understand how long their infusions might take.
I explain that their first VYLOY dose may take longer than their next infusions—and that all VYLOY infusions start at a slower rate for the first 30 to 60 minutes to help minimize the risk of adverse reactions. For example, for their first VYLOY infusion, the initial infusion rate will be 100 milligrams per meter squared per hour the first 30 to 60 minutes. If there are no adverse reactions after 30 to 60 minutes, the infusion can be increased to the Subsequent Infusion Rate shown in the Prescribing Information as tolerated.
NURSE 1: How long each infusion lasts depends on different things, including potential infusion interruptions or rate modifications. The first infusion is estimated to take a minimum of 3 and a half hours. Subsequent infusions are estimated to take a minimum of 2 and a half hours.
NURSE 2: That’s good to know because infusion days can be pretty long, so it helps to be able to give patients and caregivers an idea of what to expect.
NURSE 1: Oh! That reminds me... I always check to see if my patient is getting VYLOY and chemo on the same day. If so, VYLOY must be administered first.
NURSE 2: Thanks for all the great advice. I have a patient starting on VYLOY tomorrow. Mind if I use some of your ideas?
NURSE 1: Sure. I’ll bill you later.
(BOTH LAUGH)
NURSE 1: Just to recap, here are a few important things to remember.
Make sure the prepared VYLOY infusion bag is stored no longer than 6 hours at room temperature from the end of the preparation of the infusion bag to the completion of the infusion.
VYLOY is emetogenic. The most common adverse reactions were nausea and vomiting. Patients have to be premedicated with a combination of antiemetics like NK-1 and/or 5-HT3 receptor blockers as well as other drugs as clinically indicated. We can refer to the Prescribing Information for details.
The infusion should start at a slower rate for the first 30 to 60 minutes. If tolerated, we can gradually increase the rate as recommended.
If nausea and vomiting become Grade 2 or 3, stop the infusion. Once the symptoms are Grade 1 or less, restart it at a reduced infusion rate for the remaining infusion.
NURSE 1: You can find all of this in the VYLOY Prescribing Information.
NURSE 2: I’m so glad we talked. I know when I feel good about things, I can make a difference for my patient, too. Thanks!
NURSE 1: You’ve got this.
IMPORTANT SAFETY INFORMATION (continued)
WARNINGS AND PRECAUTIONS (continued)
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Please see Important Safety Information and full Prescribing Information at VYLOYhcp.com.
Find more videos, information on VYLOY, and other resources at VYLOYhcp.com.
TRANSCRIPT
INDICATION
VYLOY, zolbetuximab-clzb, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2, HER 2-negative, gastric or gastroesophageal junction, or GEJ, adenocarcinoma whose tumors are claudin 18.2 positive as determined by an FDA-approved test.
SELECT IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
There are Warnings and Precautions associated with VYLOY. The Warnings and Precautions for VYLOY include:
– Hypersensitivity reactions including serious anaphylaxis reactions and serious and fatal infusion-related reactions
– Severe nausea and vomiting
For more details, please listen to the Important Safety Information later in this video and see full Prescribing Information at VYLOYhcp.com.
DR. MARK LEWIS
When treating advanced gastric and gastroesophageal junction cancer, you never get a second chance to make a first-line decision. Biomarker-informed care matters because we need to know what we’re dealing with to make an appropriate therapy choice. When we can target an actionable biomarker, we can provide more individualized care for each patient.
Today, let’s talk about claudin 18.2, an important, actionable biomarker found in advanced gastric and gastroesophageal junction, or GEJ, cancer that can be targeted with VYLOY.
Claudin 18.2 is normally buried within the tight junctions of healthy gastric tissue.
Claudin 18.2 is often retained during malignant transformation and may be more exposed and accessible to antibodies when cell polarity disruptions and structure loss occur.
As disease progresses, claudin 18.2 can be expressed in lymph node metastases and in distant metastatic sites like the lungs and peritoneum.
Claudin 18.2 is highly prevalent in patients with advanced gastric or GEJ adenocarcinoma. According to estimates from 2 global Phase 3 studies, 38% of these patients are claudin 18.2 positive.
There’s a very clear definition for claudin 18.2 positivity. Thirty-eight percent represents a significant subset of patients who have this targetable biomarker which is defined as at least 75% of tumor cells showing moderate to strong membranous claudin 18 staining by IHC.
These are the patients who could potentially benefit from VYLOY, in combination with chemo, the first therapy to specifically target claudin 18.2-positive tumors.
So, when should we test for claudin 18.2? Knowing a patient’s claudin 18.2 status early can help inform our first-line treatment decisions. Claudin 18.2 is an IHC test and should be ordered at the same time as other IHC biomarkers, like HER2, for example.
National Comprehensive Cancer Network, or NCCN, Guidelines recommend claudin 18.2 testing at diagnosis of advanced adenocarcinoma. In my experience, the minimal biomarker set to consider is HER2, PD-L1, MMR, and claudin 18.2.
And how we test for claudin 18.2 is just as important as when we test. Honestly, it’s difficult to keep up with the ever-changing biomarker landscape and the tests that go with it. In this case, there’s only one test that can detect claudin 18.2, and that’s IHC. As a protein expression, claudin 18.2 is not assessable with NGS.
As we incorporate claudin 18.2 into our current biomarker testing, there are a few things to keep in mind. First, not all standardized test protocols include claudin 18.2. Check to be sure it’s included in your IHC test order. If not, you may have to order this test individually.
Next, IHC testing is quick. It typically takes about 2 to 5 days to get results. If results are taking longer, you might want to consider requesting expedited reporting or following up with your pathologist.
And finally, claudin 18.2 IHC testing is offered at labs across the country, so you have plenty of options available to you.
Having a more comprehensive understanding of a patient’s biomarker status allows us to individualize their care from the start.
With an actionable biomarker like claudin 18.2, we have the opportunity to identify patients who could have a targeted first-line treatment option with VYLOY plus chemo. When we make claudin 18.2 part of our standard testing, we expand our scope of biomarker-informed care for each patient.
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
See full Prescribing Information at VYLOYhcp.com.
Find more information at VYLOYhcp.com.
TRANSCRIPT
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze, and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs, including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough, and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Please see Important Safety Information continued in this video and full Prescribing Information at VYLOYhcp.com.
NURSE 1: As long as I’ve been an oncology nurse, it still gets to me every time I see a patient for their first cancer treatment infusion. The worry on their face breaks my heart.
NURSE 2: I feel the same. They don’t know what to expect, or how they’ll feel. It’s a lot of unknowns.
NURSE 1: But you know what? When I’ve done my homework, I can help my patients be better prepared for infusion day.
NURSE 2: I know, there are several VYLOY resources that have helped me learn what to expect and how to support my patients.
NURSE 1: You know what works for me? I took those resources and came up with an infusion-day check list to help keep me organized.
NURSE 2: How’s that work?
NURSE 1: First I start with the technical things I need to do as far as the infusion goes—like checking the IV line.
NURSE 1: I always make sure I’m using the recommended in-line filter and that I do not co-administer other drugs through the same infusion line as VYLOY.
NURSE 2: But what about patients who have central ports?
NURSE 1: From what I’ve read, no incompatibilities have been observed with closed system transfer devices or central ports with certain materials. The Prescribing Information has the full details.
NURSE 2: That’s really helpful to know.
NURSE 2: So what’s next on your checklist?
NURSE 1: I double check the prepared infusion bag and note the time. The prepared infusion bag can be kept at room temperature, 15 to 30 degrees Celsius or 59 to 86 degrees Fahrenheit, for no longer than 6 hours, from the end of the preparation of the infusion bag to the completion of the infusion. Once I’m done, I start with my patient checklist.
NURSE 2: I bet I know where that starts...
BOTH: Premedication
NURSE 1: Absolutely. These patients can be pretty sick, so I always ask how they’re feeling, especially if it’s their first infusion.
NURSE 1: If they tell me they’re nauseated or they’ve been vomiting, I make sure their symptoms are reduced to Grade 1 or less before we start the first infusion.
VYLOY is emetogenic. In clinical trials, the median time to onset of nausea and/or vomiting was within the first hour after starting the VYLOY infusion. It’s important that patients are premedicated with a combination of antiemetics like NK-1 and/or 5-HT3 receptor blockers, as well as other drugs as indicated, for the prevention of nausea and vomiting. Keep in mind that there are no contraindications for VYLOY. I always let my patients know in advance that they can expect premedication with every VYLOY infusion.
NURSE 2: I think that’s a big reassurance for the patient...to know that we’re doing everything we can to help them.
NURSE 1: Exactly...and if they do experience Grade 2 or 3 nausea or vomiting, I’ll stop the infusion until the symptoms are resolved to Grade 1 or less. Then I resume the infusion at a reduced infusion rate for the remaining infusion. If the patient experiences Grade 4 vomiting, I need to immediately stop the infusion and permanently discontinue VYLOY.
NURSE 1: The prescribing information shows the infusion rates for first and subsequent infusions. I like to use this information to help patients understand how long their infusions might take.
I explain that their first VYLOY dose may take longer than their next infusions—and that all VYLOY infusions start at a slower rate for the first 30 to 60 minutes to help minimize the risk of adverse reactions. For example, for their first VYLOY infusion, the initial infusion rate will be 100 milligrams per meter squared per hour the first 30 to 60 minutes. If there are no adverse reactions after 30 to 60 minutes, the infusion can be increased to the Subsequent Infusion Rate shown in the Prescribing Information as tolerated.
NURSE 1: How long each infusion lasts depends on different things, including potential infusion interruptions or rate modifications. The first infusion is estimated to take a minimum of 3 and a half hours. Subsequent infusions are estimated to take a minimum of 2 and a half hours.
NURSE 2: That’s good to know because infusion days can be pretty long, so it helps to be able to give patients and caregivers an idea of what to expect.
NURSE 1: Oh! That reminds me... I always check to see if my patient is getting VYLOY and chemo on the same day. If so, VYLOY must be administered first.
NURSE 2: Thanks for all the great advice. I have a patient starting on VYLOY tomorrow. Mind if I use some of your ideas?
NURSE 1: Sure. I’ll bill you later.
(BOTH LAUGH)
NURSE 1: Just to recap, here are a few important things to remember.
Make sure the prepared VYLOY infusion bag is stored no longer than 6 hours at room temperature from the end of the preparation of the infusion bag to the completion of the infusion.
VYLOY is emetogenic. The most common adverse reactions were nausea and vomiting. Patients have to be premedicated with a combination of antiemetics like NK-1 and/or 5-HT3 receptor blockers as well as other drugs as clinically indicated. We can refer to the Prescribing Information for details.
The infusion should start at a slower rate for the first 30 to 60 minutes. If tolerated, we can gradually increase the rate as recommended.
If nausea and vomiting become Grade 2 or 3, stop the infusion. Once the symptoms are Grade 1 or less, restart it at a reduced infusion rate for the remaining infusion.
NURSE 1: You can find all of this in the VYLOY Prescribing Information.
NURSE 2: I’m so glad we talked. I know when I feel good about things, I can make a difference for my patient, too. Thanks!
NURSE 1: You’ve got this.
IMPORTANT SAFETY INFORMATION (continued)
WARNINGS AND PRECAUTIONS (continued)
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Please see Important Safety Information and full Prescribing Information at VYLOYhcp.com.
Find more videos, information on VYLOY, and other resources at VYLOYhcp.com.
TRANSCRIPT
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze, and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs, including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough, and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Please see Important Safety Information continued in this video and full Prescribing Information at VYLOYhcp.com.
NURSE 1: When I first started learning about VYLOY, I was glad that there was a CLDN18.2-targeted treatment for our patients with advanced gastric or GEJ cancer.
NURSE 2: Those cancers are pretty rare, and there aren’t a lot of options for most patients. So I’m happy they have another first-line treatment choice available.
NURSE 1: I mean, we’ve never had a treatment to target this biomarker before VYLOY. And then I thought about giving my first infusion with VYLOY and chemo, and I realized…I really should study up!
(BOTH LAUGH)
NURSE 2: I know what you mean. I have a new patient starting on VYLOY soon so I’m trying to learn all I can. The first thing I wanted to know was how the treatment schedules with VYLOY and chemo would affect my patients.
NURSE 1: Me, too. I read in the Infusion and Treatment Management Guide that VYLOY can be given every two or every three weeks, so it’s great to know our patients’ VYLOY treatment aligns with their prescribed chemo schedule.
NURSE 1: In fact, we can give VYLOY and chemo on the same day, but VYLOY must be administered first.
NURSE 2: The first dose is higher at 800 milligrams per meter squared, subsequent doses are either 600 milligrams per meter squared every 3 weeks or 400 milligrams per meter squared every 2 weeks.
NURSE 2: If a patient has preexisting nausea or vomiting, the symptoms should be resolved to Grade 1 or less before we start their first VYLOY infusion. Prior to each infusion, patients should be premedicated with a combination of antiemetics to help prevent nausea and vomiting.
NURSE 1: VYLOY can only be given as an infusion, right?
NURSE 2: One hundred percent. VYLOY cannot be administered as an IV push or bolus. There’s also a matter of storage timing.
NURSE 1: What do you mean?
NURSE 2: Once the VYLOY infusion bag preparation is complete, the diluted infusion should be stored for no longer than 16 hours under refrigeration or no longer than 6 hours at room temperature.
NURSE 1: So that means we have 6 hours from the end of bag preparation to the completion of the infusion.
NURSE 2: Right. And if the infusion time exceeds the recommended storage time, we have to discard the infusion bag and prepare a new one to continue the infusion.
NURSE 1: So with that kind of timeframe, and because my patients always ask, how do you explain how long VYLOY infusions will take?
NURSE 2: I start by letting them know that to minimize risk of adverse reactions, each infusion starts at a slower rate for 30 to 60 minutes, and if tolerated, the rate is gradually increased as recommended in the Prescribing Information.
NURSE 2: The first infusion of VYLOY is estimated to take a minimum of 3 and a half hours. Each following dose may take less time. The timing really depends on potential infusion interruptions or if we have to modify the infusion rate. After the patient’s VYLOY infusion is complete, their chemo infusion could take another 2 to 3 hours based on their prescribed chemotherapy.
NURSE 1: Subsequent doses may be a little shorter but in general it can be a long day for patients. I always tell patients up front so they and their caregivers can arrange transportation, plan for snacks, and pack whatever they’ll need for the day. It’s just something I keep in mind when scheduling patients.
NURSE 2: Good plan. Everyone’s different in what they need and how they feel. Being able to set expectations for our patients and caregivers will help them have a better grasp of what their infusion day will look like.
IMPORTANT SAFETY INFORMATION (continued)
WARNINGS AND PRECAUTIONS (continued)
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Please see Important Safety Information and full Prescribing Information at VYLOYhcp.com.
Find more videos, information on VYLOY, and other resources at VYLOYhcp.com.
TRANSCRIPT
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze, and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs, including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough, and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Please see Important Safety Information continued in this video and full Prescribing Information at VYLOYhcp.com.
NURSE 1: One of the common questions I get when patients find out they’ll be receiving VYLOY plus chemo is, “What kind of side effects might I have?”
NURSE 2: I know. They worry about things like nausea and vomiting with treatment. Thankfully there are things we can do before and during treatment to help manage these side effects.
NURSE 1: Did you know in the SPOTLIGHT trial, nausea and vomiting were the most common adverse reactions in patients who received VYLOY and mFOLFOX6?
NURSE 2: That would make sense because the USPI shows that VYLOY is emetogenic. We have to be prepared because in clinical trials, the median time to onset of nausea and/or vomiting was within the first hour after starting the VYLOY infusion. Some patients may experience vomiting before they have any nausea.
I mean, some of these patients may have preexisting nausea and vomiting, and if they do, we have to make sure their symptoms are resolved to Grade 1 or less before we start their first infusion.
NURSE 1: Exactly. And before each VYLOY infusion, the Prescribing Information says to premedicate patients with a combination of antiemetics, like NK-1 receptor blockers and/or 5-HT3 receptor blockers, as well as other drugs as indicated for the prevention of nausea and vomiting. Something also to note is that there are no contraindications for VYLOY.
NURSE 2: You know, one thing that struck me as I was learning about VYLOY is that no dose reduction is recommended for adverse reactions.
NURSE 1: Adverse reactions for VYLOY are managed by reducing the infusion rate, interrupting the infusion, withholding the dose, or permanently discontinuing treatment.
NURSE 2: For hypersensitivity and infusion-related reactions, including nausea and vomiting, the VYLOY Prescribing Information provides guidance for us to follow.
For example, if a patient experiences Grade 2 or 3 infusion-related nausea and vomiting, it’s recommended to interrupt the infusion until the symptoms are resolved to Grade 1 or less. Then we can resume the infusion at a reduced infusion rate for the remaining infusion.
We’ll premedicate and administer the patient’s next infusion at the recommended infusion rates.
NURSE 1: At what point would VYLOY be discontinued because of infusion-related nausea and vomiting?
NURSE 2: If vomiting is Grade 4, it’s recommended to immediately stop the infusion, and treatment would be permanently discontinued.
NURSE 1: What about hypersensitivity and other infusion-related reactions?
NURSE 2: Good question. Besides monitoring patients for infusion-related reactions, including nausea and vomiting, we also need to monitor them for hypersensitivity reactions during the infusion and for at least 2 hours after if clinically indicated.*
*Patients should be monitored during the infusion with VYLOY for hypersensitivity reactions. Patients should be monitored for 2 hours after the completion of the infusion (or longer, if clinically indicated). This observation period after the infusion is a recommendation (not a requirement) based upon clinician’s judgement. This observation period can occur while other chemotherapy agents are being administered.
NURSE 1: You’re talking about anaphylaxis, right? So we should look for things like urticaria, repetitive cough, wheezing, tightness in the throat, or change in voice.
NURSE 2: You got it. The USPI gives us more details on what to watch out for with hypersensitivity and infusion-related reactions like nausea and vomiting.
NURSE 1: When I talk to my patients about nausea and vomiting, I like to share some of the insights I learned from the Prescribing Information and the SPOTLIGHT study.
NURSE 2: I agree. When I reviewed the package insert, I saw that nausea and vomiting should be managed during and after the infusion with antiemetics or fluid replacement. Based on severity, it is recommended to interrupt the infusion or permanently discontinue VYLOY.
NURSE 1: Keep in mind nausea and vomiting were the most common adverse reactions with VYLOY and mFOLFOX6 in the SPOTLIGHT trial, and the majority were Grades 1 and 2.
NURSE 2: Yeah, that’s pretty important for patients to know, but there’s something else I share with my patients…
NURSE 2: … and that’s the fact that nausea occurred more often during the first treatment cycle with VYLOY plus chemotherapy and decreased in incidence with subsequent cycles.
NURSE 2: The same was true for vomiting. It also occurred more frequently in the first cycle.
NURSE 1: I should point out that the Prescribing Information shows that with VYLOY plus mFOLFOX6, 16% of patients experienced Grade 3 or 4 nausea and/or vomiting in the SPOTLIGHT trial.
That being said, nausea or vomiting led to the permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in less than 4% of patients.
NURSE 2: It’s really helpful to know there are ways we can help manage adverse reactions like nausea and vomiting for our patients receiving VYLOY with chemo.
NURSE 1: And it’s important to let them know it, too.
IMPORTANT SAFETY INFORMATION (continued)
WARNINGS AND PRECAUTIONS (continued)
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Find more videos, information on VYLOY, and other resources at VYLOYhcp.com.
TRANSCRIPT
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze, and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs, including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough, and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Please see Important Safety Information continued in this video and full Prescribing Information at VYLOYhcp.com.
NURSE 1: One of the common questions I get when patients find out they’ll be receiving VYLOY plus chemo is, “What kind of side effects might I have?”
NURSE 2: I know. They worry about things like nausea and vomiting with treatment. Thankfully there are things we can do before and during treatment to help manage these side effects.
NURSE 1: Did you know in the SPOTLIGHT trial, nausea and vomiting were the most common adverse reactions in patients who received VYLOY and mFOLFOX6?
NURSE 2: That would make sense because the USPI shows that VYLOY is emetogenic. We have to be prepared because in clinical trials, the median time to onset of nausea and/or vomiting was within the first hour after starting the VYLOY infusion. Some patients may experience vomiting before they have any nausea.
I mean, some of these patients may have preexisting nausea and vomiting, and if they do, we have to make sure their symptoms are resolved to Grade 1 or less before we start their first infusion.
NURSE 1: Exactly. And before each VYLOY infusion, the Prescribing Information says to premedicate patients with a combination of antiemetics, like NK-1 receptor blockers and/or 5-HT3 receptor blockers, as well as other drugs as indicated for the prevention of nausea and vomiting. Something also to note is that there are no contraindications for VYLOY.
NURSE 2: You know, one thing that struck me as I was learning about VYLOY is that no dose reduction is recommended for adverse reactions.
NURSE 1: Adverse reactions for VYLOY are managed by reducing the infusion rate, interrupting the infusion, withholding the dose, or permanently discontinuing treatment.
NURSE 2: For hypersensitivity and infusion-related reactions, including nausea and vomiting, the VYLOY Prescribing Information provides guidance for us to follow.
For example, if a patient experiences Grade 2 or 3 infusion-related nausea and vomiting, it’s recommended to interrupt the infusion until the symptoms are resolved to Grade 1 or less. Then we can resume the infusion at a reduced infusion rate for the remaining infusion.
We’ll premedicate and administer the patient’s next infusion at the recommended infusion rates.
NURSE 1: At what point would VYLOY be discontinued because of infusion-related nausea and vomiting?
NURSE 2: If vomiting is Grade 4, it’s recommended to immediately stop the infusion, and treatment would be permanently discontinued.
NURSE 1: What about hypersensitivity and other infusion-related reactions?
NURSE 2: Good question. Besides monitoring patients for infusion-related reactions, including nausea and vomiting, we also need to monitor them for hypersensitivity reactions during the infusion and for at least 2 hours after if clinically indicated.*
*Patients should be monitored during the infusion with VYLOY for hypersensitivity reactions. Patients should be monitored for 2 hours after the completion of the infusion (or longer, if clinically indicated). This observation period after the infusion is a recommendation (not a requirement) based upon clinician’s judgement. This observation period can occur while other chemotherapy agents are being administered.
NURSE 1: You’re talking about anaphylaxis, right? So we should look for things like urticaria, repetitive cough, wheezing, tightness in the throat, or change in voice.
NURSE 2: You got it. The USPI gives us more details on what to watch out for with hypersensitivity and infusion-related reactions like nausea and vomiting.
NURSE 1: When I talk to my patients about nausea and vomiting, I like to share some of the insights I learned from the Prescribing Information and the SPOTLIGHT study.
NURSE 2: I agree. When I reviewed the package insert, I saw that nausea and vomiting should be managed during and after the infusion with antiemetics or fluid replacement. Based on severity, it is recommended to interrupt the infusion or permanently discontinue VYLOY.
NURSE 1: Keep in mind nausea and vomiting were the most common adverse reactions with VYLOY and mFOLFOX6 in the SPOTLIGHT trial, and the majority were Grades 1 and 2.
NURSE 2: Yeah, that’s pretty important for patients to know, but there’s something else I share with my patients…
NURSE 2: … and that’s the fact that nausea occurred more often during the first treatment cycle with VYLOY plus chemotherapy and decreased in incidence with subsequent cycles.
NURSE 2: The same was true for vomiting. It also occurred more frequently in the first cycle.
NURSE 1: I should point out that the Prescribing Information shows that with VYLOY plus mFOLFOX6, 16% of patients experienced Grade 3 or 4 nausea and/or vomiting in the SPOTLIGHT trial.
That being said, nausea or vomiting led to the permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in less than 4% of patients.
NURSE 2: It’s really helpful to know there are ways we can help manage adverse reactions like nausea and vomiting for our patients receiving VYLOY with chemo.
NURSE 1: And it’s important to let them know it, too.
IMPORTANT SAFETY INFORMATION (continued)
WARNINGS AND PRECAUTIONS (continued)
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Find more videos, information on VYLOY, and other resources at VYLOYhcp.com.
TRANSCRIPT
VYLOY® (zolbetuximab-clzb): A Treatment That Targets Claudin 18.2-positive (CLDN18.2+), HER2-negative Locally Advanced Unresectable, or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Descriptions of the VYLOY mechanism of action are based on preclinical data.
VYLOY is a first-in-class monoclonal antibody indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are claudin 18.2 positive as determined by an FDA-approved test.
Preclinical studies have shown that VYLOY is a claudin 18.2 directed cytolytic antibody that selectively binds to cells that express claudin 18.2, where cytotoxic immune responses are activated.
Claudin 18.2 Overview
Claudin 18.2 is present in gastric and gastroesophageal junction adenocarcinoma.
According to estimates from two global Phase 3 studies, 38% of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma are claudin 18.2-positive, which was defined as 75% or more of tumor cells demonstrating moderate to strong membranous claudin 18.2 staining by immunohistochemistry.
Claudin 18.2 may become more exposed and accessible to antibodies as gastric tumors develop.
To understand the relevance of this protein to these types of cancers, let’s take a closer look at the role of claudin 18.2 within healthy gastric mucosal tissue.
Claudin 18 in Healthy Gastric Tissue
Claudin 18 is a member of the Claudin family of transmembrane tight junction proteins.
Claudin 18.2 is the dominant claudin 18 isoform found in normal healthy gastric tissue and is typically buried within tight junctions.
As a component of tight junctions, claudins are involved in the regulation of permeability, barrier function, and polarity of epithelial layers.
Claudin 18.2 Overview
Now that we’ve explored the role of claudin 18.2 in normal tissue, let’s examine what happens in gastric adenocarcinomas.
Claudin 18.2 is often retained during malignant transformation, when cell polarity disruptions and structure loss occur.
As a result, claudin 18.2 may become more exposed and accessible to antibodies as gastric tumors develop.
Claudin 18.2 may also be expressed in lymph node metastases of gastric adenocarcinoma as well as other distant metastatic sites.
The Mechanism of Action for VYLOY [See Mechanism of Action discussion below, following presentation of some Important Safety Information for VYLOY]
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
[The Mechanism of Action for VYLOY cont.]
VYLOY is a claudin 18.2-directed cytolytic antibody that selectively binds to cells that express claudin 18.2.
When this binding occurs, cytotoxic immune responses are activated.
This is achieved through the induction of antibody-dependent cell-mediated cytotoxicity, or ADCC, and complement-dependent cytotoxicity, or CDC, leading to the destruction of cancer cells.
Let’s take a look at how VYLOY-mediated activation of ADCC and CDC may result in cancer cell depletion.
During ADCC, effector cells, such as natural killer cells, recognize antibody-targeted tumor cells and release cytotoxic molecules that cause tumor cell lysis.
At the same time, the induction of CDC gathers complement proteins at the tumor site or sites where they converge and assemble a membrane attack complex which forms pores on the tumor cell surface causing lysis of the tumor cell.
Through VYLOY-induced ADCC and CDC, claudin 18.2-positive gastric tumor cells are depleted.
Combining VYLOY and Chemotherapy
In addition to the action of VYLOY binding to claudin 18.2-positive gastric adenocarcinoma cells, it’s important to consider what happens when this cytolytic antibody is combined with chemotherapy. In the presence of the combination of chemotherapy and VYLOY, the antitumor effect has been shown to be increased compared to chemotherapy or VYLOY alone (in claudin 18.2-expressing mouse models).
VYLOY represents an approach to treating cancer, and is the first-in-class monoclonal antibody to target the claudin 18.2 biomarker, mediating the immune system mechanisms, ADCC and CDC, in locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma.
IMPORTANT SAFETY INFORMATION [CONT.]
WARNINGS AND PRECAUTIONS [CONT.]
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Please see full Prescribing Information.
Astellas is not affiliated with and does not endorse any of the listed organizations. The information provided by Astellas is for informational purposes only and is not meant to replace the advice of a healthcare professional.
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Please see full Prescribing Information.
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Please see full Prescribing Information.
TRANSCRIPT
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze, and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs, including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough, and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Please see Important Safety Information continued in this video and full Prescribing Information at VYLOYhcp.com.
NURSE 1: When I first started learning about VYLOY, I was glad that there was a CLDN18.2-targeted treatment for our patients with advanced gastric or GEJ cancer.
NURSE 2: Those cancers are pretty rare, and there aren’t a lot of options for most patients. So I’m happy they have another first-line treatment choice available.
NURSE 1: I mean, we’ve never had a treatment to target this biomarker before VYLOY. And then I thought about giving my first infusion with VYLOY and chemo, and I realized…I really should study up!
(BOTH LAUGH)
NURSE 2: I know what you mean. I have a new patient starting on VYLOY soon so I’m trying to learn all I can. The first thing I wanted to know was how the treatment schedules with VYLOY and chemo would affect my patients.
NURSE 1: Me, too. I read in the Infusion and Treatment Management Guide that VYLOY can be given every two or every three weeks, so it’s great to know our patients’ VYLOY treatment aligns with their prescribed chemo schedule.
NURSE 1: In fact, we can give VYLOY and chemo on the same day, but VYLOY must be administered first.
NURSE 2: The first dose is higher at 800 milligrams per meter squared, subsequent doses are either 600 milligrams per meter squared every 3 weeks or 400 milligrams per meter squared every 2 weeks.
NURSE 2: If a patient has preexisting nausea or vomiting, the symptoms should be resolved to Grade 1 or less before we start their first VYLOY infusion. Prior to each infusion, patients should be premedicated with a combination of antiemetics to help prevent nausea and vomiting.
NURSE 1: VYLOY can only be given as an infusion, right?
NURSE 2: One hundred percent. VYLOY cannot be administered as an IV push or bolus. There’s also a matter of storage timing.
NURSE 1: What do you mean?
NURSE 2: Once the VYLOY infusion bag preparation is complete, the diluted infusion should be stored for no longer than 16 hours under refrigeration or no longer than 6 hours at room temperature.
NURSE 1: So that means we have 6 hours from the end of bag preparation to the completion of the infusion.
NURSE 2: Right. And if the infusion time exceeds the recommended storage time, we have to discard the infusion bag and prepare a new one to continue the infusion.
NURSE 1: So with that kind of timeframe, and because my patients always ask, how do you explain how long VYLOY infusions will take?
.
NURSE 2: I start by letting them know that to minimize risk of adverse reactions, each infusion starts at a slower rate for 30 to 60 minutes, and if tolerated, the rate is gradually increased as recommended in the Prescribing Information.
NURSE 2: The first infusion of VYLOY is estimated to take a minimum of 3 and a half hours. Each following dose may take less time. The timing really depends on potential infusion interruptions or if we have to modify the infusion rate. After the patient’s VYLOY infusion is complete, their chemo infusion could take another 2 to 3 hours based on their prescribed chemotherapy.
NURSE 1: Subsequent doses may be a little shorter but in general it can be a long day for patients. I always tell patients up front so they and their caregivers can arrange transportation, plan for snacks, and pack whatever they’ll need for the day. It’s just something I keep in mind when scheduling patients.
NURSE 2: Good plan. Everyone’s different in what they need and how they feel. Being able to set expectations for our patients and caregivers will help them have a better grasp of what their infusion day will look like.
IMPORTANT SAFETY INFORMATION (continued)
WARNINGS AND PRECAUTIONS (continued)
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Please see Important Safety Information and full Prescribing Information at VYLOYhcp.com.
Find more videos, information on VYLOY, and other resources at VYLOYhcp.com.
TRANSCRIPT
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze, and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs, including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough, and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Please see Important Safety Information continued in this video and full Prescribing Information at VYLOYhcp.com.
NURSE 1: One of the common questions I get when patients find out they’ll be receiving VYLOY plus chemo is, “What kind of side effects might I have?”
NURSE 2: I know. They worry about things like nausea and vomiting with treatment. Thankfully there are things we can do before and during treatment to help manage these side effects.
NURSE 1: Did you know in the SPOTLIGHT trial, nausea and vomiting were the most common adverse reactions in patients who received VYLOY and mFOLFOX6?
NURSE 2: That would make sense because the USPI shows that VYLOY is emetogenic. We have to be prepared because in clinical trials, the median time to onset of nausea and/or vomiting was within the first hour after starting the VYLOY infusion. Some patients may experience vomiting before they have any nausea.
I mean, some of these patients may have preexisting nausea and vomiting, and if they do, we have to make sure their symptoms are resolved to Grade 1 or less before we start their first infusion.
NURSE 1: Exactly. And before each VYLOY infusion, the Prescribing Information says to premedicate patients with a combination of antiemetics, like NK-1 receptor blockers and/or 5-HT3 receptor blockers, as well as other drugs as indicated for the prevention of nausea and vomiting. Something also to note is that there are no contraindications for VYLOY.
NURSE 2: You know, one thing that struck me as I was learning about VYLOY is that no dose reduction is recommended for adverse reactions.
NURSE 1: Adverse reactions for VYLOY are managed by reducing the infusion rate, interrupting the infusion, withholding the dose, or permanently discontinuing treatment.
NURSE 2: For hypersensitivity and infusion-related reactions, including nausea and vomiting, the VYLOY Prescribing Information provides guidance for us to follow.
For example, if a patient experiences Grade 2 or 3 infusion-related nausea and vomiting, it’s recommended to interrupt the infusion until the symptoms are resolved to Grade 1 or less. Then we can resume the infusion at a reduced infusion rate for the remaining infusion.
We’ll premedicate and administer the patient’s next infusion at the recommended infusion rates.
NURSE 1: At what point would VYLOY be discontinued because of infusion-related nausea and vomiting?
NURSE 2: If vomiting is Grade 4, it’s recommended to immediately stop the infusion, and treatment would be permanently discontinued.
NURSE 1: What about hypersensitivity and other infusion-related reactions?
NURSE 2: Good question. Besides monitoring patients for infusion-related reactions, including nausea and vomiting, we also need to monitor them for hypersensitivity reactions during the infusion and for at least 2 hours after if clinically indicated.*
*Patients should be monitored during the infusion with VYLOY for hypersensitivity reactions. Patients should be monitored for 2 hours after the completion of the infusion (or longer, if clinically indicated). This observation period after the infusion is a recommendation (not a requirement) based upon clinician’s judgement. This observation period can occur while other chemotherapy agents are being administered.
NURSE 1: You’re talking about anaphylaxis, right? So we should look for things like urticaria, repetitive cough, wheezing, tightness in the throat, or change in voice.
NURSE 2: You got it. The USPI gives us more details on what to watch out for with hypersensitivity and infusion-related reactions like nausea and vomiting.
NURSE 1: When I talk to my patients about nausea and vomiting, I like to share some of the insights I learned from the Prescribing Information and the SPOTLIGHT study.
NURSE 2: I agree. When I reviewed the package insert, I saw that nausea and vomiting should be managed during and after the infusion with antiemetics or fluid replacement. Based on severity, it is recommended to interrupt the infusion or permanently discontinue VYLOY.
NURSE 1: Keep in mind nausea and vomiting were the most common adverse reactions with VYLOY and mFOLFOX6 in the SPOTLIGHT trial, and the majority were Grades 1 and 2.
NURSE 2: Yeah, that’s pretty important for patients to know, but there’s something else I share with my patients …
NURSE 2: … and that’s the fact that nausea occurred more often during the first treatment cycle with VYLOY plus chemotherapy and decreased in incidence with subsequent cycles.
NURSE 2: The same was true for vomiting. It also occurred more frequently in the first cycle.
NURSE 1: I should point out that the Prescribing Information shows that with VYLOY plus mFOLFOX6, 16% of patients experienced Grade 3 or 4 nausea and/or vomiting in the SPOTLIGHT trial.
That being said, nausea or vomiting led to the permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in less than 4% of patients.
NURSE 2: It’s really helpful to know there are ways we can help manage adverse reactions like nausea and vomiting for our patients receiving VYLOY with chemo.
NURSE 1: And it’s important to let them know it, too.
IMPORTANT SAFETY INFORMATION (continued)
WARNINGS AND PRECAUTIONS (continued)
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Find more videos, information on VYLOY, and other resources at VYLOYhcp.com.
TRANSCRIPT
INDICATION
VYLOY, zolbetuximab-clzb, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2, HER 2-negative, gastric or gastroesophageal junction, or GEJ, adenocarcinoma whose tumors are claudin 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
Please see Important Safety Information continued in this video and full Prescribing Information at VYLOYhcp.com.
DR. MARK LEWIS
For years, chemotherapy alone has been the standard of care for advanced gastric and gastroesophageal junction, or GEJ, cancers and now, we’re getting a better understanding about the biomarkers driving a patient’s cancer type and targeting treatment in innovative ways.
Today I want to talk about VYLOY, the first claudin 18.2 targeted therapy.
VYLOY was studied in combination with chemotherapy in two double-blind, randomized phase 3 clinical trials—SPOTLIGHT and GLOW.
[In general, the PFS and OS endpoint results were consistent across SPOTLIGHT and GLOW. Results from the Phase 3 trial with CAPOX chemotherapy are available at VYLOYhcp.com.]
The trials included first-line patients with claudin 18.2-positive, HER2-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. Claudin 18.2-positivity was defined as at least 75% of tumor cells demonstrating moderate to strong membranous claudin 18 staining by IHC.
While both trials are important and results were consistent between the two, today we’ll only be looking at SPOTLIGHT.
SPOTLIGHT evaluated survival with VYLOY in combination with mFOLFOX6 compared to mFOLFOX6 alone.
Patients were randomized one-to-one and treatment continued until disease progression or unacceptable toxicity.
Progression-free survival was the major efficacy outcome in the study. The primary analysis showed that patients receiving VYLOY plus mFOLFOX6 achieved a median PFS of 10.6 months compared to 8.7 months on mFOLFOX6 alone. That translates to a 25% reduction in the risk of progression or death and a statistically significant PFS improvement vs mFOLFOX6 alone.
Now let’s take a look at the results for median overall survival, which was an additional efficacy outcome in the study.
The primary analysis also showed a statistically significant OS benefit, with patients receiving VYLOY plus mFOLFOX6 achieving 18.2 months median OS vs 15.5 with mFOLFOX6 alone. There was also a 25% reduction in the risk of death vs mFOLFOX6 alone.
Now let’s take a look at the follow-up analyses, which were prespecified analyses of long-term PFS and OS rates.
It’s important to keep in mind that these analyses are not included in the US Full Prescribing Information. They are from prespecified landmark analyses with approximately 1 year of additional follow-up. They were not statistically powered to detect differences between treatment arms or adjusted for multiplicity; therefore, no conclusions can be drawn.
The PFS follow-up estimates analysis included PFS rates at 12, 24, and 36 months. As you can see, at 36 months, PFS rate estimates were 22% for patients randomized to VYLOY + mFOLFOX6 and 10% for patients randomized to mFOLFOX6 alone according to Kaplan-Meier calculation.
Now let’s take a look at the estimated long-term OS rates based on prespecified landmark analyses, which included overall survival rates at 12, 24, 36, and 48 months.
At 48 months, 16% of patients randomized to VYLOY + mFOLFOX6 and 11% of patients randomized to mFOLFOX6 alone were alive according to Kaplan-Meier calculations.
Another important treatment consideration for VYLOY is the safety profile. Let’s take a look at what occurred in the SPOTLIGHT trial.
The most common adverse reactions reported with VYLOY included nausea, vomiting, decreased appetite, and peripheral edema.
Of those, nausea and vomiting occurred most frequently and happened most often during the first cycle of treatment.
There are steps that can be taken for the prevention and management of nausea and vomiting.
Prior to each infusion, premedication is recommended with a combination of antiemetics. Per the VYLOY USPI, there are no known contraindications including with other medications. The NCCN considers Zolbetuximab (VYLOY®) to be highly emetogenic, with the preferred recommendation to use a 4-drug antiemetic regimen.
No dose reduction for VYLOY is recommended. Adverse reactions are instead managed by adjusting the infusion, whether it’s slowing the rate, interrupting the infusion, or, if necessary, discontinuing.
Now that we have an idea of the impact VYLOY + mFOLFOX6 could make, let’s talk through a hypothetical patient scenario.
Let’s consider a patient like this. When I diagnose advanced disease, I test for NCCN-recommended biomarkers, including claudin 18.2, to get a better understanding of their cancer.
Comprehensive testing is critical for a patient at this stage, because when I can identify they are claudin 18.2-positive and HER2-negative, VYLOY + chemo becomes an eligible first-line targeted treatment option.
Until recently, there haven’t been CLDN18.2-directed options for this type of patient—VYLOY + chemo is the first.
So as you think about your advanced gastric and GEJ cancer patients, I encourage you to keep the data I’ve shared and a few other key points in mind.
First, it’s important to test for CLDN18.2 up front, so you know what you’re dealing with and can make an informed first-line treatment decision quickly.
Next, the VYLOY plus mFOLFOX6 regimen should be given with antiemetics for the prevention and management of nausea and vomiting as recommended by the Prescribing Information and supportive guidelines.
Finally, having a meaningful first conversation with patients can help them feel more confident in what to expect and the potential benefits of treatment with VYLOY + chemo.
And remember when you test for Claudin 18.2, you are taking a critical step toward identifying a patient who may benefit from the addition of a targeted first-line treatment.
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count,decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable ormetastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
See full Prescribing Information at VYLOYhcp.com.
Find more information at VYLOYhcp.com.
TRANSCRIPT
INDICATION
VYLOY, zolbetuximab-clzb, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2, HER 2-negative, gastric or gastroesophageal junction, or GEJ, adenocarcinoma whose tumors are claudin 18.2 positive as determined by an FDA-approved test.
SELECT IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
There are Warnings and Precautions associated with VYLOY. The Warnings and Precautions for VYLOY include:
– Hypersensitivity reactions including serious anaphylaxis reactions and serious and fatal infusion-related reactions
– Severe nausea and vomiting
For more details, please listen to the Important Safety Information later in this video and see full Prescribing Information at VYLOYhcp.com.
DR. MARK LEWIS
When treating advanced gastric and gastroesophageal junction cancer, you never get a second chance to make a first-line decision. Biomarker-informed care matters because we need to know what we’re dealing with to make an appropriate therapy choice. When we can target an actionable biomarker, we can provide more individualized care for each patient.
Today, let's talk about claudin 18.2, an important, actionable biomarker found in advanced gastric and gastroesophageal junction, or GEJ, cancer that can be targeted with VYLOY.
Claudin 18.2 is normally buried within the tight junctions of healthy gastric tissue.
Claudin 18.2 is often retained during malignant transformation and may be more exposed and accessible to antibodies when cell polarity disruptions and structure loss occur.
As disease progresses, claudin 18.2 can be expressed in lymph node metastases and in distant metastatic sites like the lungs and peritoneum.
Claudin 18.2 is highly prevalent in patients with advanced gastric or GEJ adenocarcinoma. According to estimates from 2 global Phase 3 studies, 38% of these patients are claudin 18.2 positive.
There’s a very clear definition for claudin 18.2 positivity. Thirty-eight percent represents a significant subset of patients who have this targetable biomarker which is defined as at least 75% of tumor cells showing moderate to strong membranous claudin 18 staining by IHC.
These are the patients who could potentially benefit from VYLOY, in combination with chemo, the first therapy to specifically target claudin 18.2-positive tumors.
So, when should we test for claudin 18.2? Knowing a patient’s claudin 18.2 status early can help inform our first-line treatment decisions. Claudin 18.2 is an IHC test and should be ordered at the same time as other IHC biomarkers, like HER2, for example.
National Comprehensive Cancer Network, or NCCN, Guidelines recommend claudin 18.2 testing at diagnosis of advanced adenocarcinoma. In my experience, the minimal biomarker set to consider is HER2, PD-L1, MMR, and claudin 18.2.
And how we test for claudin 18.2 is just as important as when we test. Honestly, it’s difficult to keep up with the ever-changing biomarker landscape and the tests that go with it. In this case, there’s only one test that can detect claudin 18.2, and that’s IHC. As a protein expression, claudin 18.2 is not assessable with NGS.
As we incorporate claudin 18.2 into our current biomarker testing, there are a few things to keep in mind. First, not all standardized test protocols include claudin 18.2. Check to be sure it’s included in your IHC test order. If not, you may have to order this test individually.
Next, IHC testing is quick. It typically takes about 2 to 5 days to get results. If results are taking longer, you might want to consider requesting expedited reporting or following up with your pathologist.
And finally, claudin 18.2 IHC testing is offered at labs across the country, so you have plenty of options available to you.
Having a more comprehensive understanding of a patient’s biomarker status allows us to individualize their care from the start.
With an actionable biomarker like claudin 18.2, we have the opportunity to identify patients who could have a targeted first-line treatment option with VYLOY plus chemo. When we make claudin 18.2 part of our standard testing, we expand our scope of biomarker-informed care for each patient.
INDICATION
VYLOY® (zolbetuximab-clzb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
See full Prescribing Information at VYLOYhcp.com.
Find more information on VYLOY, CLDN18.2 testing, and lab locations at VYLOYhcp.com.
TRANSCRIPT
VYLOY® (zolbetuximab-clzb): A Treatment That Targets Claudin 18.2-positive (CLDN18.2+), HER2-negative Locally Advanced Unresectable, or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Descriptions of the VYLOY mechanism of action are based on preclinical data.
VYLOY is a first-in-class monoclonal antibody indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are claudin 18.2 positive as determined by an FDA-approved test.
Preclinical studies have shown that VYLOY is a claudin 18.2 directed cytolytic antibody that selectively binds to cells that express claudin 18.2, where cytotoxic immune responses are activated.
Claudin 18.2 Overview
Claudin 18.2 is present in gastric and gastroesophageal junction adenocarcinoma.
According to estimates from two global Phase 3 studies, 38% of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma are claudin 18.2-positive, which was defined as 75% or more of tumor cells demonstrating moderate to strong membranous claudin 18.2 staining by immunohistochemistry.
Claudin 18.2 may become more exposed and accessible to antibodies as gastric tumors develop.
To understand the relevance of this protein to these types of cancers, let’s take a closer look at the role of claudin 18.2 within healthy gastric mucosal tissue.
Claudin 18 in Healthy Gastric Tissue
Claudin 18 is a member of the Claudin family of transmembrane tight junction proteins.
Claudin 18.2 is the dominant claudin 18 isoform found in normal healthy gastric tissue and is typically buried within tight junctions.
As a component of tight junctions, claudins are involved in the regulation of permeability, barrier function, and polarity of epithelial layers.
Claudin 18.2 Overview
Now that we’ve explored the role of claudin 18.2 in normal tissue, let’s examine what happens in gastric adenocarcinomas.
Claudin 18.2 is often retained during malignant transformation, when cell polarity disruptions and structure loss occur.
As a result, claudin 18.2 may become more exposed and accessible to antibodies as gastric tumors develop.
Claudin 18.2 may also be expressed in lymph node metastases of gastric adenocarcinoma as well as other distant metastatic sites.
The Mechanism of Action for VYLOY [See Mechanism of Action discussion below, following presentation of some Important Safety Information for VYLOY]
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.
[The Mechanism of Action for VYLOY cont.]
VYLOY is a claudin 18.2-directed cytolytic antibody that selectively binds to cells that express claudin 18.2.
When this binding occurs, cytotoxic immune responses are activated.
This is achieved through the induction of antibody-dependent cell-mediated cytotoxicity, or ADCC, and complement-dependent cytotoxicity, or CDC, leading to the destruction of cancer cells.
Let’s take a look at how VYLOY-mediated activation of ADCC and CDC may result in cancer cell depletion.
During ADCC, effector cells, such as natural killer cells, recognize antibody-targeted tumor cells and release cytotoxic molecules that cause tumor cell lysis.
At the same time, the induction of CDC gathers complement proteins at the tumor site or sites where they converge and assemble a membrane attack complex which forms pores on the tumor cell surface causing lysis of the tumor cell.
Through VYLOY-induced ADCC and CDC, claudin 18.2-positive gastric tumor cells are depleted.
Combining VYLOY and Chemotherapy
In addition to the action of VYLOY binding to claudin 18.2-positive gastric adenocarcinoma cells, it’s important to consider what happens when this cytolytic antibody is combined with chemotherapy.
In the presence of the combination of chemotherapy and VYLOY, the antitumor effect has been shown to be increased compared to chemotherapy or VYLOY alone (in claudin 18.2-expressing mouse models).
VYLOY represents an approach to treating cancer, and is the first-in-class monoclonal antibody to target the claudin 18.2 biomarker, mediating the immune system mechanisms, ADCC and CDC, in locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma.
IMPORTANT SAFETY INFORMATION [CONT.]
WARNINGS AND PRECAUTIONS [CONT.]
Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.
ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.
Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.
SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.
Please see full Prescribing Information.
