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*Fluoropyrimidine- and platinum-containing chemotherapy.1
SPOTLIGHT: PROGRESSION-FREE SURVIVAL (PFS)
Number of events: 146 (51.6%) with VYLOY + mFOLFOX6 vs 167 (59.2%) with mFOLFOX6 alone.1
*PFS was assessed per RECIST v1.1 by independent review committee (IRC).1
†Based on Kaplan-Meier estimate.1
CI=confidence interval; HR=hazard ratio; RECIST=Response Evaluation Criteria in Solid Tumors.
SPOTLIGHT: OVERALL SURVIVAL (OS)
Number of events: 149 (52.7%) with VYLOY + mFOLFOX6 vs 177 (62.8%) with mFOLFOX6 alone.1
*Based on Kaplan-Meier estimate.1
SPOTLIGHT: RESPONSE DATA
| Objective Response Rate (ORR) | VYLOY + mFOLFOX6 (n=283)* | PLACEBO + mFOLFOX6 (n=282)* |
|---|---|---|
| ORR (CR + PR) (%) (95% CI)†‡ | 40.3% (34.5, 46.3) | 39.7% (34.0, 45.7) |
| Complete response rate (%) | 14 (4.9) | 8 (2.8) |
| Partial response rate (%) | 100 (35.3) | 104 (36.9) |
| Duration of response (DOR) | VYLOY + mFOLFOX6 (N=114) | PLACEBO + mFOLFOX6 (N=112) |
|---|---|---|
| Median in months (95% CI)‡ | 10.3 (8.3, 10.9) | 10.5 (7.7, 13.3) |
*211 patients in each treatment arm had measurable disease, according to RECIST v1.1, at baseline.2
†ORR based on binomial distribution (Clopper-Pearson).1
‡ORR and DOR were assessed per RECIST v1.1 by IRC.1
SPOTLIGHT: PROGRESSION-FREE SURVIVAL (PFS)
The results below are from prespecified landmark analyses* with additional ~1 year of follow-up.† These analyses were not statistically powered to detect differences between treatment arms or adjusted for multiplicity; therefore, no conclusions can be drawn.
Median follow-up for PFS: 18.0 months (95% CI, 15.3 to 23.3) in the VYLOY + mFOLFOX6 group and 17.9 months (95% CI, 14.8 to 23.8) in the placebo + mFOLFOX6 group.3
Number of events: 159 with VYLOY + mFOLFOX6 vs 187 with mFOLFOX6 alone.3
*Landmark analysis (or "landmark survival analysis") is a survival-analysis approach that assesses how a patient's status at a predefined time point (the "landmark") relates to the subsequent occurrence of an event of interest, including only patients who remain event-free up to that time.4
†Time from the primary analysis.3
‡PFS was assessed per RECIST v1.1 by IRC.3
§Based on Kaplan-Meier method.3
SPOTLIGHT: OVERALL SURVIVAL (OS)
The results below are from prespecified landmark analyses* with additional ~1 year of follow-up.† These analyses were not statistically powered to detect differences between treatment arms or adjusted for multiplicity; therefore, no conclusions can be drawn.
Median follow-up for OS: 33.3 months (95% CI, 29.3 to 37.6) in the VYLOY + mFOLFOX6 group and 31.4 months (95% CI, 28.7 to 36.2) in the placebo + mFOLFOX6 group.3
Number of events: 197 with VYLOY + mFOLFOX6 vs 217 with mFOLFOX6 alone.3
*Landmark analysis (or "landmark survival analysis") is a survival-analysis approach that assesses how a patient's status at a predefined time point (the "landmark") relates to the subsequent occurrence of an event of interest, including only patients who remain event-free up to that time.4
†Time from the primary analysis.3
‡Based on Kaplan-Meier method.3
This is an exploratory, post hoc analysis that was not prespecified in the statistical analysis plan. No formal hypothesis testing was performed, and no P values are reported. Results are descriptive and hypothesis-generating only.
*Relative exposure intensity=(actual cumulative dose/planned cumulative dose for duration of treatment) X 100%.
SPOTLIGHT: PROGRESSION-FREE SURVIVAL (PFS)
This is an exploratory, post hoc analysis that was not prespecified in the statistical analysis plan. No formal hypothesis testing was performed, and no P values are reported. Results are descriptive and hypothesis-generating only.
This ad hoc analysis was performed on the prespecified landmark analyses,† which included an additional ~1 year of follow-up from the primary analysis.‡
Median follow-up for PFS: 18.0 months (95% CI, 15.3 to 23.3) in the VYLOY + mFOLFOX6 group and 17.9 months (95% CI, 14.8 to 23.8) in the placebo + mFOLFOX6 group.3
Number of events: 159 with VYLOY + mFOLFOX6 vs 187 with mFOLFOX6 alone.3
*Patients were censored due to inadequate dose exposure (dose interruption of any study drug with <75% relative exposure intensity of VYLOY or placebo) or early discontinuation (withdrawal of any study drug with VYLOY or placebo within 63 days) due to nausea and vomiting. The total number of randomized patients remained unchanged. Patients meeting censoring criteria were included in the analysis but contributed follow-up time only up to the point of censoring.5
†Landmark analysis (or “landmark survival analysis”) is a survival-analysis approach that assesses how a patient’s status at a predefined time point (the “landmark”) relates to the subsequent occurrence of an event of interest, including only patients who remain event-free up to that time.4
‡The cutoff date for the primary analysis was September 2022 and September 2023 for the exploratory ad hoc analysis.2,3
SPOTLIGHT: OVERALL SURVIVAL (OS)
This is an exploratory, post hoc analysis that was not prespecified in the statistical analysis plan. No formal hypothesis testing was performed, and no P values are reported. Results are descriptive and hypothesis-generating only.
This ad hoc analysis was performed on the prespecified landmark analyses,† which included an additional ~1 year of follow-up from the primary analysis.‡
Median follow-up for OS: 33.3 months (95% CI, 29.3 to 37.6) in the VYLOY + mFOLFOX6 group and 31.4 months (95% CI, 28.7 to 36.2) in the placebo + mFOLFOX6 group.3
Number of events: 197 with VYLOY + mFOLFOX6 vs 217 with mFOLFOX6 alone.3
*Patients were censored due to inadequate dose exposure (dose interruption of any study drug with <75% relative exposure intensity of VYLOY or placebo) or early discontinuation (withdrawal of any study drug with VYLOY or placebo within 63 days) due to nausea and vomiting. The total number of randomized patients remained unchanged. Patients meeting censoring criteria were included in the analysis but contributed follow-up time only up to the point of censoring.5
†Landmark analysis (or “landmark survival analysis”) is a survival-analysis approach that assesses how a patient’s status at a predefined time point (the “landmark”) relates to the subsequent occurrence of an event of interest, including only patients who remain event-free up to that time.4
‡The cutoff date for the primary analysis was September 2022 and September 2023 for the exploratory ad hoc analysis.2,3
SPOTLIGHT PRIMARY ANALYSIS: STUDY DESIGN
ELIGIBILITY CRITERIA2¶
SELECT EXCLUSION CRITERIA1,2¶
Study population: Median age was 61 (range: 20-86). 62% were male. 48% were White, 34% Asian, 3.0% American Indian or Alaska, 1.2% Black or African American, 4.1% other, 9% race unknown or missing; 78% non-Hispanic or Latino, 13% Hispanic or Latino, and 10% ethnicity missing. 98% had ECOG performance status (PS) of 0 or 1. 76% had gastric cancer, 24% had GEJ cancer, 84% were metastatic, 16% were locally advanced, and 29% had prior gastrectomy. Subsequent anticancer therapy: 135 (48%) patients in the VYLOY + mFOLFOX6 arm and 148 (53%) patients in the placebo + mFOLFOX6 arm.1 Lauren classification: 35% diffuse, 24% intestinal, 8% mixed, 16% unknown, 16% other, and 1% missing.2
*Claudin 18.2+ (CLDN18.2 positive) is defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining by IHC.2
†HER2- tumor as determined by local or central testing.2
‡Patients were randomized 1:1 to receive VYLOY in combination with mFOLFOX6 (n=283) or placebo in combination with mFOLFOX6 (n=282). VYLOY was administered intravenously at an initial dose of 800 mg/m2 (Day 1 of Cycle 1) followed by subsequent doses of 600 mg/m2 every 3 weeks in combination with up to 12 treatments (4 cycles) of mFOLFOX6 (oxaliplatin 85 mg/m2, folinic acid (leucovorin or local equivalent) 400 mg/m2, fluorouracil 400 mg/m2 given as a bolus and fluorouracil 2400 mg/m2 given as a continuous infusion) administered on Days 1, 15, and 29 of a 42-day cycle. After 12 treatments, patients were allowed to continue treatment with VYLOY, 5-fluorouracil and folinic acid (leucovorin or local equivalent) at the discretion of the investigator, until progression of disease or unacceptable toxicity.1
§Treatment continued until RECIST v1.1-defined progression of disease as determined by an independent review committee (IRC).1
||Assessed per RECIST v1.1 by IRC.1
¶Does not include all patient inclusion and exclusion criteria for the SPOTLIGHT trial.2
CLDN18.2=claudin 18.2; CNS=central nervous system; ECOG=Eastern Cooperative Oncology Group; G/GEJ=gastric/gastroesophageal junction; HER2=human epidermal growth factor receptor 2.
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.1 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 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.
To see more educational videos on VYLOY, click here.
SPOTLIGHT PRIMARY ANALYSIS: SAFETY
| ADVERSE REACTION | VYLOY with mFOLFOX6 (n=279) | PLACEBO with mFOLFOX6 (n=278) | |||
|---|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | ||
| Gastrointestinal disorders | Nausea | 82 | 16 | 61 | 7 |
| Vomiting | 67 | 16 | 36 | 6 | |
| Metabolism and nutrition disorders | Decreased appetite | 47 | 6 | 34 | 3.2 |
| General disorders and administration site conditions | Peripheral edema | 18 | 0.7 | 9 | 0 |
| LABORATORY ABNORMALITY | VYLOY with mFOLFOX6* | PLACEBO with mFOLFOX6* | ||
|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | |
| Albumin decreased | 78 | 4.4 | 47 | 1.1 |
| Potassium decreased | 28 | 11 | 21 | 6 |
| Glucose decreased | 45 | 0.4 | 35 | 0.4 |
| Sodium decreased | 29 | 5 | 21 | 2.9 |
*The denominator used to calculate the rate varied from 271 to 272 based on the number of patients with a baseline value and at least 1 post-treatment value.
†Safety results, including ad hoc assessments of incidence, timing, and management of nausea/vomiting, are descriptive and observational in nature. These analyses do not control for potential confounders (e.g., antiemetic regimen selection, steroid use, infusion modifications) and therefore should not be interpreted as demonstrating causality or comparative effectiveness.5
*Median time to the first occurrence of nausea/vomiting on cycle 1, day 1 was 50.5 minutes after the start of the first infusion (range 0-371 minutes, n=90). Median time to onset was evaluated among patients who experienced nausea/vomiting and for whom time-of-onset data were available.5
GLOW: PROGRESSION-FREE SURVIVAL (PFS)
Number of events: 137 (53.9%) with VYLOY + CAPOX vs 172 (68.0%) with CAPOX alone.1
*PFS was assessed per RECIST v1.1 by independent review committee (IRC).1
†Based on Kaplan-Meier estimate.1
CI=confidence interval; HR=hazard ratio; RECIST=Response Evaluation Criteria in Solid Tumors.
GLOW: OVERALL SURVIVAL (OS)
Number of events: 144 (56.7%) with VYLOY + CAPOX vs 174 (68.8%) with CAPOX alone.1
*Based on Kaplan-Meier estimate.1
GLOW: RESPONSE DATA
| Objective Response Rate (ORR) | VYLOY + CAPOX (n=254)* | PLACEBO + CAPOX (n=253)* |
|---|---|---|
| ORR (CR + PR) (%) (95% CI)†‡ | 32.3% (26.6, 38.4) | 31.2% (25.6, 37.3) |
| Complete response rate (%) | 6 (2.4) | 2 (0.8) |
| Partial response rate (%) | 76 (29.9) | 77 (30.4) |
| Duration of response (DOR) | VYLOY + CAPOX (N=82) | PLACEBO + CAPOX (N=79) |
|---|---|---|
| Median in months (95% CI)‡ | 8.3 (6.3, 11.4) | 6.2 (6.0, 7.6) |
*195 patients in the VYLOY + CAPOX arm and 205 in the placebo + CAPOX arm had measurable disease, based on central assessment, at baseline.7
†ORR based on binomial distribution (Clopper-Pearson).1
‡ORR and DOR were assessed per RECIST v1.1 by IRC.1
GLOW: PROGRESSION-FREE SURVIVAL (PFS)
The results below are from prespecified landmark analyses* with additional ~1 year of follow-up.† These analyses were not statistically powered to detect differences between treatment arms or adjusted for multiplicity; therefore, no conclusions can be drawn.
Median follow-up for PFS: 20.6 months (95% CI, 15.2 to 23.6) in the VYLOY + CAPOX group and 23.5 months (95% CI, 10.4 to 25.8) in the placebo + CAPOX group.3
Number of events: 153 with VYLOY + CAPOX vs 182 with CAPOX alone.3
*Landmark analysis (or "landmark survival analysis") is a survival-analysis approach that assesses how a patient's status at a predefined time point (the "landmark") relates to the subsequent occurrence of an event of interest, including only patients who remain event-free up to that time.4
†Time from the primary analysis.3
‡PFS was assessed per RECIST v1.1 by IRC.3
§Based on Kaplan-Meier method.3
GLOW: OVERALL SURVIVAL (OS)
The results below are from prespecified landmark analyses* with additional ~1 year of follow-up.† These analyses were not statistically powered to detect differences between treatment arms or adjusted for multiplicity; therefore, no conclusions can be drawn.
Median follow-up for OS: 31.7 months (95% CI, 28.2 to 33.7) in the VYLOY + CAPOX group and 33.0 months (95% CI, 29.7 to 35.9) in the placebo + CAPOX group.3
Number of events: 180 with VYLOY + CAPOX vs 207 with CAPOX alone.3
*Landmark analysis (or "landmark survival analysis") is a survival-analysis approach that assesses how a patient's status at a predefined time point (the "landmark") relates to the subsequent occurrence of an event of interest, including only patients who remain event-free up to that time.4
†Time from the primary analysis.3
‡Based on Kaplan-Meier method.3
This is an exploratory, post hoc analysis that was not prespecified in the statistical analysis plan. No formal hypothesis testing was performed, and no P values are reported. Results are descriptive and hypothesis-generating only.
*Relative exposure intensity=(actual cumulative dose/planned cumulative dose for duration of treatment) X 100%.
GLOW: PROGRESSION-FREE SURVIVAL (PFS)
This is an exploratory, post hoc analysis that was not prespecified in the statistical analysis plan. No formal hypothesis testing was performed, and no P values are reported. Results are descriptive and hypothesis-generating only.
This ad hoc analysis was performed on the prespecified landmark analyses,† which included an additional ~1 year of follow-up from the primary analysis.‡
Median follow-up for PFS: 20.6 months (95% CI, 15.2 to 23.6) in the VYLOY + CAPOX group and 23.5 months (95% CI, 10.4 to 25.8) in the placebo + CAPOX group.3
Number of events: 153 with VYLOY + CAPOX vs 182 with CAPOX alone3
*Patients were censored due to inadequate dose exposure (dose interruption of any study drug with <75% relative exposure intensity of VYLOY or placebo) or early discontinuation (withdrawal of any study drug with VYLOY or placebo within 63 days) due to nausea and vomiting. The total number of randomized patients remained unchanged. Patients meeting censoring criteria were included in the analysis but contributed follow-up time only up to the point of censoring.5
†Landmark analysis (or “landmark survival analysis”) is a survival-analysis approach that assesses how a patient’s status at a predefined time point (the “landmark”) relates to the subsequent occurrence of an event of interest, including only patients who remain event-free up to that time.4
‡The cutoff date for the primary analysis was October 2022 and January 2024 for the exploratory ad hoc analysis.3,7
GLOW: OVERALL SURVIVAL (OS)
This is an exploratory, post hoc analysis that was not prespecified in the statistical analysis plan. No formal hypothesis testing was performed, and no P values are reported. Results are descriptive and hypothesis-generating only.
This ad hoc analysis was performed on the prespecified landmark analyses,† which included an additional ~1 year of follow-up from the primary analysis.‡
Median follow-up for OS: 31.7 months (95% CI, 28.2 to 33.7) in the VYLOY + CAPOX group and 33.0 months (95% CI, 29.7 to 35.9) in the placebo + CAPOX group.3
Number of events: 180 with VYLOY + CAPOX vs 207 with CAPOX alone.3
*Patients were censored due to inadequate dose exposure (dose interruption of any study drug with <75% relative exposure intensity of VYLOY or placebo) or early discontinuation (withdrawal of any study drug with VYLOY or placebo within 63 days) due to nausea and vomiting. The total number of randomized patients remained unchanged. Patients meeting censoring criteria were included in the analysis but contributed follow-up time only up to the point of censoring.5
†Landmark analysis (or “landmark survival analysis”) is a survival-analysis approach that assesses how a patient’s status at a predefined time point (the “landmark”) relates to the subsequent occurrence of an event of interest, including only patients who remain event-free up to that time.4
‡The cutoff date for the primary analysis was October 2022 and January 2024 for the exploratory ad hoc analysis.3,7
GLOW PRIMARY ANALYSIS: STUDY DESIGN
ELIGIBILITY CRITERIA7¶
SELECT EXCLUSION CRITERIA1,7¶
Study population: Median age was 60 (range: 21-83). 62% were male. 62% were Asian, 36% White, 1.4% race missing; 95% non-Hispanic or Latino, 3.4% Hispanic or Latino, and 1.4% ethnicity missing. 99% had ECOG performance status (PS) of 0 or 1. 84% had primary gastric cancer, 16% had primary GEJ cancer, 88% were metastatic, 12% were locally advanced, and 27% had prior gastrectomy.1 Lauren classification: 37% diffuse, 15% intestinal, 8% mixed, 28% unknown, 12% other, and 1% missing.7
*Claudin 18.2+ (CLDN18.2 positive) is defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining by IHC.7
†HER2- tumor as determined by local or central testing.7
‡Patients were randomized 1:1 to receive VYLOY in combination with CAPOX (n=254) or placebo in combination with CAPOX (n=253). VYLOY was administered intravenously at an initial dose of 800 mg/m2 (Day 1 of Cycle 1) followed by subsequent doses of 600 mg/m2 every 3 weeks in combination with up to 8 treatments (8 cycles) of CAPOX administered on Day 1 (oxaliplatin 130 mg/m2) and on Days 1 to 14 (capecitabine 1000 mg/m2) of a 21-day cycle. After 8 treatments of oxaliplatin, patients were allowed to continue treatment of VYLOY and capecitabine at the discretion of the investigator, until progression of disease or unacceptable toxicity.1
§Treatment continued until RECIST v1.1-defined progression of disease as determined by an independent review committee (IRC).1
||Assessed per RECIST v1.1 by IRC.1
¶Does not include all patient inclusion and exclusion criteria for the GLOW trial.7
CLDN18.2=claudin 18.2; CNS=central nervous system; ECOG=Eastern Cooperative Oncology Group; G/GEJ=gastric/gastroesophageal junction; HER2=human epidermal growth factor receptor 2.
GLOW PRIMARY ANALYSIS: SAFETY
| ADVERSE REACTION | VYLOY with CAPOX (n=254) | PLACEBO with CAPOX (n=249) | |||
|---|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | ||
| Gastrointestinal disorders | Nausea | 69 | 9 | 50 | 2.4 |
| Vomiting | 66 | 12 | 31 | 3.6 | |
| Metabolism and nutrition disorders | Decreased appetite | 41 | 7 | 34 | 1.6 |
| Blood and lymphatic system disorders | Neutropenia | 20 | 7 | 14 | 2.8 |
| Investigations | Weight decreased | 20 | 0.4 | 10 | 0.4 |
| LABORATORY ABNORMALITY | VYLOY with CAPOX* | PLACEBO with CAPOX* | ||
|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | |
| Albumin decreased | 66 | 3.8 | 47 | 1.7 |
| Leukocytes decreased | 66 | 6 | 60 | 8 |
| Neutrophils decreased | 76 | 21 | 70 | 14 |
| Glucose decreased | 24 | 0 | 18 | 0 |
*The denominator used to calculate the rate varied from 237 to 238 based on the number of patients with a baseline value and at least 1 post-treatment value.
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.
Please see Important Safety Information and full Prescribing Information at VYLOYhcp.com.
Find more videos, information on VYLOY, and other resources at VYLOYhcp.com.
To see more educational videos on VYLOY, click here.
*Fluoropyrimidine- and platinum-containing chemotherapy.1
IHC=immunohistochemistry.
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.
References:
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.
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