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In advanced* gastric/GEJ cancer,

Testing for CLDN18.2
reveals potential candidates
for VYLOY + chemo.1†

*Locally advanced unresectable or metastatic.1

†Fluoropyrimidine- and platinum-containing chemotherapy.1

CLDN18.2=claudin 18.2; GEJ=gastroesophageal junction.

Woman holding photo of herself with Claudin 18.2+ written on it
Woman holding photo of herself with Claudin 18.2+ written on it

*Locally advanced unresectable or metastatic.1

†Fluoropyrimidine- and platinum-containing chemotherapy.1

CLDN18.2=claudin 18.2; GEJ=gastroesophageal junction.

CLDN18.2 is a highly prevalent biomarker in advanced G/GEJ adenocarcinoma2-12

Image showing 38% of patients with advanced gastric/GEJ cancer are CLDN18.2 positive
Image showing 38% of patients with advanced gastric/GEJ cancer are CLDN18.2 positive

CLDN18.2+ is defined as a ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining by IHC.2,3

Biomarker prevalence estimates from select studies

Prevalence data can vary among studies due to tumor heterogeneity, differences in patient population, clinical trial methodology, and diagnostic assays used.2-12

BiomarkerCLDN18.22,3
(positive)†		PD-L14,8-11
(variable due to
multiple factors)‡		HER25-7
(positive)		MSI10-12
(MSI-high)§
Prevalence38%CPS ≥1: 67-82%
CPS ≥5: 29-60%
CPS ≥10: 16-49%		14-22%3-7%

*Locally advanced unresectable or metastatic.1

†Data from 2 global randomized Phase 3 studies: SPOTLIGHT, which included 2,403 assessable patients, of which 922 were CLDN18.2 positive; and GLOW, which included 2,104 assessable patients, of which 808 were CLDN18.2 positive.2,3

‡CPS thresholds are still being explored. Data are from randomized controlled trials and real-world retrospective medical records studies.4,8-11

§MSI-H prevalence varies by stage of disease. Data shown are from patients with advanced disease.10-12

CLDN18.2=claudin 18.2; CPS=combined positive score; HER2=human epidermal growth factor receptor 2; MSI=microsatellite instability; NGS=next generation sequencing; 
PD-L1=programmed death-ligand 1.

See what Dr. Mark Lewis has to say about CLDN18.2 and why testing for this biomarker is so critical.

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.

To see more educational videos on VYLOY, click here.

Only IHC testing identifies CLDN18.21

Image showing CLDN18.2 is only detectable via IHC

As a protein expression, CLDN18.2 is detectable by IHC and is not detectable by next generation sequencing (NGS).13

NCCN biomarker testing recommendations

National Comprehensive Cancer Network® (NCCN®)

CLDN18.2 testing by IHC is recommended at the time of diagnosis if advanced or metastatic adenocarcinoma is documented or suspected.14,15*

Diagram showing when to test for CLDN18.2 in locally advanced or metastatic gastric/GEJ adenocarcinoma
Diagram showing when to test for CLDN18.2 in locally advanced or metastatic gastric/GEJ adenocarcinoma

Adapted with permission from NCCN Guidelines; Palliative management for gastric/gastroesophageal adenocarcinoma, available at nccn.org.14,15

*This is a summary of relevant portions of the NCCN Guidelines®. Please see the full NCCN Guidelines for Gastric Cancer and Esophageal and Esophagogastric Junction Cancers at NCCN.org.14,15

†NGS should be considered via validated assay.

‡If not previously performed.

§Chemoradiation applies only to locally unresectable gastric cancer if not previously received.

||Treatment guidelines differ for gastric cancer with peritoneal carcinoma as only disease.

NCCN=National Comprehensive Cancer Network® (NCCN®).

Test all patients at diagnosis for CLDN18.21

Illustration of a checked box above CLDN18.2

Order CLDN18.2 IHC testing at the same time as HER2 and other biomarkers.2-4,16

Illustration of a question mark inside of a box

Check to be sure CLDN18.2 is included in your IHC test order, as you may need to individually request this test.

Illustration of a speeding clock

IHC testing should take 2-5 days.17,18 If results take longer, request expedited reporting.

Illustration showing an outline of the United States

CLDN18.2 testing is offered at labs cross the country. Find a lab here. 

Start a conversation about CLDN18.2 testing

Download a brochure with helpful information to discuss with your pathologist.

Evaluating CLDN18.2 Status

VENTANA CLDN18 (43-14A) RxDx Assay is FDA approved as a companion diagnostic to identify patients who may be candidates for treatment with VYLOY (zolbetuximab-clzb) + chemotherapy. 1,19

CLDN18.2 status is evaluated using both membranous staining intensity and percentage of viable tumor cells stained.19

  • The immunohistochemical staining in gastric cancer tissue shows the full spectrum of membrane staining from no staining to weak, moderate, and/or strong membrane staining19
  • The relative percentage of neoplastic cells staining at moderate and strong membrane intensity determines the CLDN18.2 IHC status of either positive or negative for the case19
  • CLDN18.2 is maintained in metastatic progression, suggesting that accurate CLDN18.2 assessment may be performed from both primary tumor and metastases20-23

Membrane staining of tumor cells24

Photo showing an example of no CLDN18 staining
Photo showing an example of no CLDN18 staining

NO STAINING

Photo showing an example of weak CLDN18 staining
Photo showing an example of weak CLDN18 staining

WEAK STAINING

Photo showing an example of moderate CLDN18 staining
Photo showing an example of moderate CLDN18 staining

MODERATE STAINING

Photo showing an example of strong CLDN18 staining
Photo showing an example of strong CLDN18 staining

STRONG STAINING

The clinical cutoff is ≥75% viable tumor cells demonstrating moderate-to-strong membranous CLDN18 staining above background.19*

*Test results of the VENTANA CLDN18 (43-14A) RxDx Assay should be interpreted by a qualified pathologist in conjunction with histological examination, relevant clinical information, and proper controls.19

Testing locations

Testing is available at various labs throughout the United States. The following locations are testing sites that offer the VENTANA CLDN18 (43-14A) RxDx Assay. These listings may not be inclusive of all locations. All trademarks are the properties of their respective owners. Astellas is not affiliated with and does not endorse any of the listed laboratories. The information provided by Astellas is for informational purposes only.

Ameripath Memphis

Beth Israel Deaconess Medical Center

Capital Digestive Care

Caris Life Sciences

Cedars-Sinai Medical Center

Cleveland Clinic

Columbia University

CSI Laboratories

Dana Farber Cancer Institute

Duke University Medical Center

Foundation Medicine

Guardant Health, Inc.

Henrico Doctors' Hospital (HCA Richmond)

Inform Diagnostics

Intermountain Health

Johns Hopkins Medicine

LabCorp

Mass General Cancer Center

Mayo Clinic

MD Anderson Cancer Center

Memorial Sloan Kettering Cancer Center

Moffitt Cancer Center

NeoGenomics

New York University Medical Center

Northwestern University Medical Center

Path Group

PhenoPath

Providence Portland Medical Center

Stanford University Medical Center

Sylvester Cancer Center

Tempus

Tricore

UC San Francisco

University of Iowa Medical Center

University of Kansas Medical Center

University of Michigan Medical Center

University of Pittsburgh Medical Center (UPMC)

University of Rochester Medical Center

University of Vermont Medical Center

University of Wisconsin

Vanderbilt University Medical Center

Yale University Medical Center

Resources for the lab

Assay education

Learn how to detect CLDN18.2+ cells in G/GEJ tumors with the VENTANA CLDN18 (43-14A) RxDx Assay.1,19 Explore the eLearning Module on cancerdiagnosticeducation.com.

Expand your lab’s test offerings

Visit go.roche.com/CLDN18 to learn more about the FDA-approved assay indicated to help identify patients who may be candidates for VYLOY + chemo.

Woman in lavender blouse inside a Claudin 18.2-positive frame

Find out how VYLOY targets CLDN18.2 and mediates cytotoxic immune system mechanisms.1

INDICATION

IMPORTANT SAFETY 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.

References:

  1. VYLOY. Package insert. Northbrook, IL: Astellas Pharma US, Inc; 2025.
  2. Shitara K, Lordick F, Bang YJ, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet 2023;401(10389):1655-68. Errata in: Lancet 2023;402(10398):290; Lancet 2024;403(10421):30.
  3. Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med 2023;29(8):2133-41.
  4. Fuchs CS, Özgüroğlu M, Bang YJ, et al. Pembrolizumab versus paclitaxel for previously treated PD‑L1‑positive advanced gastric or gastroesophageal junction cancer: 2‑year update of the randomized phase 3 KEYNOTE‑061 trial. Gastric Cancer 2022;25(1):197-206.
  5. Van Cutsem E, Bang YJ, Feng-Yi F, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer 2015;18(3):476-84.
  6. Janjigian YY, Werner D, Pauligk C, et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA international collaborative analysis. Ann Oncol 2012;23(10):2656-62.
  7. Kim WH, Gomez-Izquierdo L, Vilardell F, et al. HER2 status in gastric and gastroesophageal junction cancer: results of the large, multinational HER-EAGLE study. Appl Immunohistochem Mol Morphol 2018;26(4):239-45.
  8. Schoemig-Markiefka B, Eschbach J, Scheel AH, et al. Optimized PD-L1 scoring of gastric cancer. Gastric Cancer 2021;24(5):1115-22.
  9. Mehta R, Liepa AM, Zheng S, Chatterjee A. Real-world molecular biomarker testing patterns and results for advanced gastroesophageal cancers in the United States. Curr Oncol 2023;30(2):1869-81.
  10. Shitara K, Ajani J, Moehler M, et al. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature 2022;603(7903):942-48.
  11. Rha SY, Oh D-Y, Yañez P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 2023;24(11):1181-95.
  12. Chao J, Fuchs CS, Shitara K, et al. Assessment of pembrolizumab therapy for the treatment of microsatellite instability-high gastric or gastroesophageal junction cancer among patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 clinical trials. JAMA Oncol 2021;7(6):895-902.
  13. El-Deiry WS, Goldberg RM, Lenz HJ, et al. The current state of molecular testing in the treatment of patients with solid tumors, 2019. CA Cancer J Clin 2019;69(4):305-43.
  14. Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer V.2.2026. © 2026 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  15. Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Junction Cancers V.2.2026. 
© 2026 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  16. Abrahao-Machado LF, Scapulatempo-Neto C. HER2 testing in gastric cancer: an update. World J Gastroenterol 2016;22(19):4619-25.
  17. Krigsfeld GS, Prince EA, Pratt J, et al. Analysis of real-world PD-L1 IHC 28-8 and 22C3 pharmDx assay utilisation, turnaround times and analytical concordance across multiple tumour types. J Clin Pathol. 2020;73(10):656-664.
  18. Mubarak M. Quality assurance in histopathology laboratories. J Clin Transl Pathol. 2023;3(4):184-189.
  19. VENTANA CLDN18 (43-14A) assay [package insert]. Tucson, AZ: Ventana Medical Systems, Inc.
  20. Sahin U, Koslowski M, Dhaene K, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res 2008;14(23):7624-34.
  21. Coati I, Lotz G, Fanelli GN, et al. Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled cases. Br J Cancer 2019;121(3):257-63.
  22. Pellino A, Brignola S, Riello E, et al. Association of CLDN18 protein expression with clinicopathological features and prognosis in advanced gastric and gastroesophageal junction adenocarcinomas. J Pers Med (Epub) 10-26-2021.
  23. Rohde C, Yamaguchi R, Mukhina S, Sahin U, Itoh K, Türeci Ö. Comparison of claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma. Jpn J Clin Oncol 2019;49(9):870-6.
  24. VENTANA CLDN18 (43-14A) RxDx assay interpretation guide for gastric adenocarcinoma including gastroesophageal junction (GEJ). Tucson, AZ: 2024.

INDICATION

IMPORTANT SAFETY 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.

References:

  1. VYLOY. Package insert. Northbrook, IL: Astellas Pharma US, Inc; 2025.
  2. Shitara K, Lordick F, Bang YJ, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet 2023;401(10389):1655-68. Errata in: Lancet 2023;402(10398):290; Lancet 2024;403(10421):30.
  3. Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med 2023;29(8):2133-41.
  4. Fuchs CS, Özgüroğlu M, Bang YJ, et al. Pembrolizumab versus paclitaxel for previously treated PD‑L1‑positive advanced gastric or gastroesophageal junction cancer: 2‑year update of the randomized phase 3 KEYNOTE‑061 trial. Gastric Cancer 2022;25(1):197-206.
  5. Van Cutsem E, Bang YJ, Feng-Yi F, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer 2015;18(3):476-84.
  6. Janjigian YY, Werner D, Pauligk C, et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA international collaborative analysis. Ann Oncol 2012;23(10):2656-62.
  7. Kim WH, Gomez-Izquierdo L, Vilardell F, et al. HER2 status in gastric and gastroesophageal junction cancer: results of the large, multinational HER-EAGLE study. Appl Immunohistochem Mol Morphol 2018;26(4):239-45.
  8. Schoemig-Markiefka B, Eschbach J, Scheel AH, et al. Optimized PD-L1 scoring of gastric cancer. Gastric Cancer 2021;24(5):1115-22.
  9. Mehta R, Liepa AM, Zheng S, Chatterjee A. Real-world molecular biomarker testing patterns and results for advanced gastroesophageal cancers in the United States. Curr Oncol 2023;30(2):1869-81.
  10. Shitara K, Ajani J, Moehler M, et al. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature 2022;603(7903):942-48.
  11. Rha SY, Oh D-Y, Yañez P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 2023;24(11):1181-95.
  12. Chao J, Fuchs CS, Shitara K, et al. Assessment of pembrolizumab therapy for the treatment of microsatellite instability-high gastric or gastroesophageal junction cancer among patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 clinical trials. JAMA Oncol 2021;7(6):895-902.
  13. El-Deiry WS, Goldberg RM, Lenz HJ, et al. The current state of molecular testing in the treatment of patients with solid tumors, 2019. CA Cancer J Clin 2019;69(4):305-43.
  14. Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer V.2.2026. © 2026 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  15. Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Junction Cancers V.2.2026. 
© 2026 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  16. Abrahao-Machado LF, Scapulatempo-Neto C. HER2 testing in gastric cancer: an update. World J Gastroenterol 2016;22(19):4619-25.
  17. Krigsfeld GS, Prince EA, Pratt J, et al. Analysis of real-world PD-L1 IHC 28-8 and 22C3 pharmDx assay utilisation, turnaround times and analytical concordance across multiple tumour types. J Clin Pathol. 2020;73(10):656-664.
  18. Mubarak M. Quality assurance in histopathology laboratories. J Clin Transl Pathol. 2023;3(4):184-189.
  19. VENTANA CLDN18 (43-14A) assay [package insert]. Tucson, AZ: Ventana Medical Systems, Inc.
  20. Sahin U, Koslowski M, Dhaene K, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res 2008;14(23):7624-34.
  21. Coati I, Lotz G, Fanelli GN, et al. Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled cases. Br J Cancer 2019;121(3):257-63.
  22. Pellino A, Brignola S, Riello E, et al. Association of CLDN18 protein expression with clinicopathological features and prognosis in advanced gastric and gastroesophageal junction adenocarcinomas. J Pers Med (Epub) 10-26-2021.
  23. Rohde C, Yamaguchi R, Mukhina S, Sahin U, Itoh K, Türeci Ö. Comparison of claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma. Jpn J Clin Oncol 2019;49(9):870-6.
  24. VENTANA CLDN18 (43-14A) RxDx assay interpretation guide for gastric adenocarcinoma including gastroesophageal junction (GEJ). Tucson, AZ: 2024.