Zolbetuximab

Initial US Approval

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 (G) or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLAUDIN (CLDN) 18.2–positive as determined by an FDA-approved test.¹

800 mg/m2: initial, 100 mg/m2/hr for 30-60 min; increase to 200-265 mg/m2/hr if initial rate tolerated.1

600 mg/m2 (every 3 weeks): initial, 75 mg/m2/hr for 30-60 min; increase to 150-265 mg/m2/hr if initial rate tolerated.1
400 mg/m2 (every 2 weeks): initial, 50 mg/m2/hr for 30-60 min; increase to 100-200 mg/m2/hr if initial rate tolerated.1

NOTE: If infusion time exceeds recommended storage time (see Storage), discard infusion bag and prepare a new infusion bag to continue infusion.1

No dose reduction is recommended. Adverse reactions are managed by reducing the infusion rate, interrupting the infusion, withholding the dose, or permanently discontinuing zolbetuximab, as described in the package insert.¹

Key Inclusion Criteria: Eligible patients were at least 18 years of age, negative pregnancy status, not a woman of childbearing potential or who agrees to follow protocol-based contraceptive guidance, histologically confirmed G/GEJ carcinoma, radiologically confirmed locally advanced unresectable or metastatic disease within 28 days before randomization, CLDN18.2 expression in tumor ≥75%, HER2-negative, ECOG 0-1, and various other criteria listed in the study protocol.
Treatment: Zolbetuximab, 800 mg/m², followed by 600 mg/m² plus CAPOX for eight 21-day cycles versus placebo plus CAPOX.

Key Inclusion Criteria: Eligible patients were at least 18 years of age, negative pregnancy status, not a woman of childbearing potential or who agrees to follow protocol-based contraceptive guidance, histologically confirmed G/GEJ carcinoma, radiologically confirmed locally advanced unresectable or metastatic disease within 28 days before randomization, CLDN18.2 expression in tumor ≥75%, HER2-negative, ECOG 0-1, and various other criteria listed in the study protocols.
Treatment: Zolbetuximab,800 mg/m2, followed by 600 mg/m2 (every 3 weeks) plus mFOLFOX6 (every 2 weeks) or placebo plus mFOLFOX6.

Common Adverse Reactions (≥15%): The most frequently reported any-grade adverse events (AE) were nausea (69%), vomiting (66%), decreased appetite (41%), and decreased weight (20%).
Common Laboratory Abnormalities (≥15%): The most frequently reported any-grade laboratory abnormalities were decreased neutrophils (76%), decreased albumin (66%), decreased leukocytes (66%), decreased glucose (24%), and neutropenia (20%).
Dosage Interruption Due to AEs: 55%
Permanent Discontinuation Due to AEs: 19%

Common Adverse Reactions (≥15%): The most frequently reported any-grade AEs were nausea (82%), vomiting (67%), decreased appetite (47%), and peripheral edema (18%).
Common Laboratory Abnormalities (≥15%): The most frequently reported any-grade laboratory abnormalities were decreased albumin (78%), decreased glucose (45%), decreased sodium (29%), and decreased potassium (28%).
Dosage Interruption Due to AEs: 75%
Permanent Discontinuation Due to AEs: 20%

Vyloy (Zolbetuximab-Clzb). Prescribing information. AstellasPharma US, Inc; 2024. Accessed March 3, 2025. https://www.astellas.com/us/system/files/vyloy_pi.pdf
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):2133-2141. doi:10.1038/s41591-023-02465-7
Shitara K, Van Cutsem E, Lordick F, et al. Final overall survival results from phase 3 SPOTLIGHT study evaluating zolbetuximab + mFOLFOX6 as first-line (1L) treatment for patients (pts) with claudin 18 isoform 2 (CLDN18.2)+, HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. JCO. 2024;42(suppl 16):4036-4036. doi:10.1200/JCO.2024.42.16_suppl.4036
Shimozaki K, Ooki A, Yamahata Y, et al. Managing zolbetuximab-induced nausea and vomiting: a proposal for a pragmatic approach in clinical practice. ESMO Gastrointestinal Oncology. 2025;7:100128. doi:10.1016/j.esmogo.2024.100128
Vyloy Infusion and Treatment Management Guide. Astellas Pharma US, Inc; 2024. Accessed March 3, 2025. https://www.vyloyhcp.com/content/dam/zolbebranded/hcp/us/en/pdf/mat-us-zol-2024-00343-vyloy-infusion-treatment-management-guide.pdf
NCCN Clinical Practice Guidelines in Oncology. Antiemesis, version 2.2024. Accessed March 3, 2025. https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf