Zolbetuximab

Zolbetuximab-clzb is a claudin 18.2 (CLDN18.2)-directed cytolytic antibody that depletes CLDN18.2-positive cells via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Zolbetuximab-clzb in combination with chemotherapy had increased antitumor activity in CLDN18.2-expressing mouse tumor models compared to zolbetuximab-clzb or chemotherapy alone.

• VYLOY, 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 [see Dosage and Administration ( 2.1 ) and Clinical Studies ( 14 )]. VYLOY is a claudin 18.2-directed cytolytic antibody and is indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy 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 adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test ( 1 ).

• None. None.contraindicated

• Administer by intravenous infusion only . Do not administer VYLOY as an intravenous push or bolus. ( 2.6 ) • The recommended first dose of VYLOY is 800 mg/m 2 followed by 600 mg/m 2 every 3 weeks or 400 mg/m 2 every 2 weeks. ( 2.3 ) 2.1 Patient Selection Select adult patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors are CLDN18.2 positive (defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining) for treatment with VYLOY in combination with fluoropyrimidine- and platinum-containing chemotherapy using an FDA-approved test [see Clinical Studies ( 14 )]. Information on FDA-approved tests for the detection of CLDN18.2 is available at https://www.fda.gov/CompanionDiagnostics . 2.2 Prior to Administration If a patient is experiencing nausea and/or vomiting prior to administration of VYLOY, the symptoms should be resolved to Grade ≤1 before administering the first infusion. Premedication Prior to each infusion of VYLOY, premedicate patients with a combination of antiemetics (e.g., NK-1 receptor blockers and/or 5-HT3 receptor blockers, as well as other drugs as indicated) for the prevention of nausea and vomiting [see Warnings and Precautions ( 5.2 )]. 2.3 Recommended Dosage Administer VYLOY in combination with fluoropyrimidine- and platinum-containing chemotherapy as follows: • First dose: 800 mg/m 2 intravenously. • Subsequent doses: o 600 mg/m 2 intravenously every 3 weeks, or o 400 mg/m 2 intravenously every 2 weeks.

• Hypersensitivity reactions including serious anaphylaxis reactions and serious and fatal infusion-related reactions have occurred. Monitor patients during and for at least 2 hours after infusion with VYLOY. Interrupt, slow the rate of infusion or permanently discontinue VYLOY based on severity and type of reaction. Premedicate with antihistamines for subsequent infusions after a hypersensitivity reaction. ( 2.4 , 5.1 ) • Severe nausea and vomiting: Premedicate patients with antiemetics prior to each infusion. Interrupt or permanently discontinue VYLOY based on the severity of the nausea and/or vomiting. Manage patients during and after infusion with antiemetics or fluid replacement. ( 2.4 , 5.2 ) 5.1 Hypersensitivity reactions, including anaphylaxis reactions, and infusion related reactions 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.

The following serious adverse reactions are described elsewhere in the labeling: • Hypersensitivity Reactions, including anaphylaxis, and infusion related reactions [see Warnings and Precautions ( 5.1 )] . • Severe Nausea and Vomiting [see Warnings and Precautions ( 5.2 )] . The most common adverse reactions (≥15%) for VYLOY in combination with mFOLFOX6 or CAPOX were nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia. The most common laboratory abnormalities (≥15%) for VYLOY in combination with mFOLFOX6 or CAPOX were 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 ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary There are no data with VYLOY use in pregnant women to inform any drug-associated risks. Embryo-fetal toxicity was not observed in pregnant mice intravenously administered zolbetuximab-clzb [see Data] . VYLOY should only be given to a pregnant woman if the benefit outweighs the potential risk. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data In an embryo-fetal development toxicity study, zolbetuximab-clzb was intravenously administered to pregnant mice during the period of organogenesis and did not result in embryo-fetal toxicity at doses up to 300 mg/kg (approximately 1.9 times the recommended clinical dose based on AUC). Zolbetuximab-clzb crossed the placental barrier resulting in higher fetal serum concentrations on Day 18 of gestation than maternal serum concentrations on Day 16 of gestation. 8.2 Lactation Risk Summary There are no data on the presence of zolbetuximab-clzb in human milk, the effects on the breastfed child, or the effects on milk production.

Metabolism

Following a 2-hour intravenous infusion, zolbetuximab-clzb exhibited dose-proportional pharmacokinetics at doses ranging from 33 mg/m 2 to 1000 mg/m 2 (0.04 times to 1.25 times the recommended first dose). When administered at a first dose of 800 mg/m 2 followed by subsequent doses of 600 mg/m 2 every 3 weeks, steady state was achieved by 18 weeks with a geometric mean (coefficient of variation [CV]%) C max of 415 (22%) mcg/mL and AUC tau of 3149 (37%) day•mcg/mL.

• Oct 18, 2024BLABLA761365Astellas

1. 1Nausea42840%
2. 2Vomiting20219%
3. 3Decreased Appetite15014%
4. 4Ascites948.7%
5. 5Hypoalbuminaemia898.3%
6. 6Malignant Neoplasm Progression807.4%
7. 7Blood Albumin Decreased645.9%
8. 8Diarrhoea635.8%
9. 9Oedema Peripheral524.8%
10. 10Malaise484.5%
11. 11Neutrophil Count Decreased474.4%
12. 12Myelosuppression444.1%
13. 13Abdominal Pain434.0%
14. 14Fatigue393.6%
15. 15Pyrexia383.5%

The 10 most recently updated of 23 ClinicalTrials.gov registrations naming Zolbetuximab as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of Zolbetuximab Together With Pembrolizumab and Chemotherapy in Adults With Gastric Cancer
  Recruiting · Phase 3 · Interventional · 500 enrolled · Astellas Pharma Global Development, Inc.
  NCT06901531updated 2026-06-05
• A Study of Zolbetuximab (IMAB362) in Adults With Pancreatic Cancer
  Active not recruiting · Phase 2 · Interventional · 393 enrolled · Astellas Pharma Global Development, Inc.
  NCT03816163updated 2026-06-04
• Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2
  Recruiting · Phase 3 · Interventional · 2,130 enrolled · AstraZeneca
  NCT07431281updated 2026-05-27
• Timing of Minimally Invasive Local Treatment After First-Line Systemic Therapy in Oligometastatic Esophageal or Gastric Adenocarcinoma
  Recruiting · Phase 2 · Phase 3 · Interventional · 290 enrolled · Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  NCT07000253updated 2026-05-07
• A Study to Compare Zolbetuximab (IMAB362) and Chemotherapy With Placebo and Chemotherapy in Adults With Gastric Cancer.
  Active not recruiting · Phase 3 · Interventional · 565 enrolled · Astellas Pharma Global Development, Inc.
  NCT03504397updated 2026-05-04
• A Study of Zolbetuximab (IMAB362) Plus CAPOX Compared With Placebo Plus CAPOX as First-line Treatment of Subjects With Claudin (CLDN) 18.2-positive, HER2-negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (GLOW).
  Active not recruiting · Phase 3 · Interventional · 507 enrolled · Astellas Pharma Global Development, Inc.
  NCT03653507updated 2026-04-17
• A Study of Zolbetuximab (IMAB362) in Adults With Gastric Cancer
  Active not recruiting · Phase 2 · Interventional · 143 enrolled · Astellas Pharma Global Development, Inc.
  NCT03505320updated 2026-04-03
• A Study to Observe the Safety of VYLOY (Zolbetuximab) in People in South Korea With Gastric or Gastroesophageal Junction Cancer.
  Recruiting · Observational · 377 enrolled · Astellas Pharma Korea, Inc.
  NCT06902545updated 2026-03-11
• Real-WorlD ZolbetUximab in Patients With HER-2 Negative and CLaudin 18.2 PosItive MetastatiC AdEnocarcinoma
  Recruiting · Observational · 70 enrolled · European Institute of Oncology
  NCT07427992updated 2026-02-23
• Synergistic Effects of PD-1 Antibody and Chemotherapy/Targeted Therapy Followed by Surgery-centric Local Treatment in Patients With Limited-metastatic Gastric Cancer
  Recruiting · Phase 2 · Interventional · 84 enrolled · Shanghai Zhongshan Hospital
  NCT06468280updated 2026-01-21

Frequently asked questions

How does Zolbetuximab work?

Zolbetuximab-clzb is a claudin 18.2 (CLDN18.2)-directed cytolytic antibody that depletes CLDN18.2-positive cells via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Zolbetuximab-clzb in combination with chemotherapy had increased antitumor activity in CLDN18.2-expressing mouse tumor models compared to zolbetuximab-clzb or chemotherapy alone.

What is Zolbetuximab used for?

According to FDA labeling, Zolbetuximab carries indications including: VYLOY, 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 [see Dosage and Administration ( 2.1 ) and Clinical Studies ( 14 )]. VYLOY is a claudin 18.2-directed cytolytic antibody and is indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy 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 adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test ( 1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Zolbetuximab?

Zolbetuximab is classified as Other monoclonal antibodies and antibody drug conjugates, Claudin 18.2-directed Cytolytic Antibody, Antibody-Surface Protein Interactions, Claudin 18.2-directed Antibody Interactions, Increased Cellular Death.

What are the brand names for Zolbetuximab?

Zolbetuximab is marketed under brand names including Vyloy.

What are the contraindications for Zolbetuximab?

Zolbetuximab labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.