Vyloy Zolbetuximab for Injection

1. Indications and Usage
Gastric Cancer:
Indicated for the treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma, whose tumors are positive for claudin (CLDN) 18.2, as detected by an FDA-approved test, in combination with fluoropyrimidine- and platinum-containing chemotherapy.
2. Dosage and Administration
Patient Selection:
Select patients whose tumors are CLDN18.2 positive (defined as ≥75% of tumor cells showing moderate-to-strong membranous CLDN18 immunohistochemical staining) using an FDA-approved test.
Pre-medication:
Administer a combination of antiemetics (e.g., NK-1 receptor antagonist and/or 5-HT3 receptor antagonist, plus dexamethasone) before each zolbetuximab infusion to prevent nausea and vomiting.
Recommended Dosage:
Regimen A (Every 3 Weeks): Initial dose of 800 mg/m² (Cycle 1, Day 1), followed by 600 mg/m² every 3 weeks.
Regimen B (Every 2 Weeks): Initial dose of 800 mg/m² (Cycle 1, Day 1), followed by 400 mg/m² every 2 weeks.
Administration: Administer via intravenous infusion over 90 minutes (first infusion) or 60 minutes (subsequent infusions). Do not administer as an intravenous push or bolus.
3. Mechanism of Action
CLDN18.2 Targeting:
Zolbetuximab is a chimeric (mouse/human) IgG1 monoclonal antibody that binds to the extracellular domains of CLDN18.2.
Physiological Effect:
It induces CLDN18.2-positive cell depletion through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), leading to tumor cell lysis.
4. Safety and Warnings
Infusion-Related Reactions (IRR):
Severe and fatal IRRs have been reported. Monitor patients closely during and for at least 1 hour after infusion. Interrupt infusion for Grade 2 reactions; permanently discontinue for Grade 3/4 reactions.
Severe Nausea and Vomiting:
Zolbetuximab has a significant emetogenic potential, particularly during the first cycle of treatment.
5. Adverse Reactions
Most Common (≥15%):
Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, weight loss, hypersensitivity, and pyrexia.
Laboratory Abnormalities:
Neutrophil count decreased, leukocyte count decreased, albumin decreased, creatinine increased, hemoglobin decreased, and lymphocyte count decreased.
6. Drug Interactions
Chemotherapy Agents:
When used in combination with platinum or fluoropyrimidine-based chemotherapy, monitor for overlapping toxicities (e.g., myelosuppression, gastrointestinal toxicity).
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Zolbetuximab-clzb.
Storage:
Store at 2°C to 8°C (36°F to 46°F). Do not freeze or shake vigorously.