Zolbetuximab (trade name: VYLOY) is a cytolytic antibody-drug targeting Claudin 18.2 (CLDN18.2). It was first approved for marketing in the United States in 2024. This drug is indicated as first-line therapy for locally advanced unresectable or metastatic HER2-negative adenocarcinoma of the stomach/gastroesophageal junction, and patients must be confirmed as CLDN18.2-positive (moderate to strong membranous staining in ≥75% of tumor cells) by an FDA-approved test.
Recommended Dosage and Administration of Zolbetuximab
1. Dosing Regimen
Zolbetuximab is administered via intravenous infusion; intravenous push or rapid injection is strictly prohibited. The specific dosage regimens are as follows:
(1) First Dose
The dose for the first infusion of zolbetuximab is 800 mg/m², administered intravenously.
(2) Subsequent Maintenance Doses
The subsequent maintenance doses of zolbetuximab are either 600 mg/m² once every 3 weeks or 400 mg/m² once every 2 weeks.
(3) Treatment Duration
Treatment should be continued until disease progression or the occurrence of intolerable toxicities.
2. Combined Medication Instructions
Zolbetuximab must be used in combination with chemotherapy regimens containing fluoropyrimidine and platinum:
(1) mFOLFOX6 regimen: Oxaliplatin + Leucovorin + 5-Fluorouracil
(2) CAPOX regimen: Oxaliplatin + Capecitabine
(3) Administration Sequence
If zolbetuximab is administered on the same day as chemotherapy, zolbetuximab must be infused first.
Pre-Administration Preparation for Zolbetuximab
1. Patient Screening Criteria
Before receiving zolbetuximab treatment, patients must be confirmed by the FDA-approved VENTANA CLDN18 (43-14A) RxDx test to meet the following criteria:
(1) HER2-negative status;
(2) CLDN18.2-positive (moderate to strong membranous staining in ≥75% of tumor cells).
2. Pre-Treatment Measures
(1) Antiemetic Pre-Treatment
Antiemetic drugs (such as NK-1 receptor antagonists, 5-HT3 receptor antagonists, etc.) must be used in combination before each infusion of zolbetuximab.
(2) Nausea and Vomiting Management
If a patient has Grade ≥2 nausea/vomiting before zolbetuximab administration, the infusion can only start after the symptoms subside to Grade ≤1.
Dose Adjustment Principles for Zolbetuximab
1. Management of Allergic/Infusion Reactions
(1) Grade 2 Reactions: Pause the infusion of zolbetuximab; resume the infusion at a reduced rate after symptoms subside to Grade ≤1.
(2) Grade 3-4 Reactions or Allergic Reactions: Permanently discontinue zolbetuximab and provide standard emergency treatment.
(3) Subsequent Prevention: After an allergic reaction occurs, patients must take antihistamines in advance before subsequent infusions of zolbetuximab.
2. Management of Nausea and Vomiting
(1) Grade 3 Nausea/Vomiting: Pause zolbetuximab administration until symptoms subside.
(2) Grade 4 Nausea/Vomiting: Permanently discontinue zolbetuximab.
(3) Cycle Management: Intensify the antiemetic regimen, with special attention to the first treatment cycle.
(4) Record the frequency and severity of nausea and vomiting.
Infusion Management Standards for Zolbetuximab
1. Infusion Rate Control
(1) First Infusion
Initial rate: 100 mg/m²/hour (for the first 30-60 minutes);
Rate after tolerance is confirmed: May be increased to 200-265 mg/m²/hour.
(2) Subsequent Infusions
Every-3-week regimen: Initial rate of 75 mg/m²/hour; after tolerance is confirmed, 150-265 mg/m²/hour;
Every-2-week regimen: Initial rate of 50 mg/m²/hour; after tolerance is confirmed, 100-200 mg/m²/hour.
2. Infusion Monitoring Requirements
(2) Full-Course Monitoring:
During the infusion of zolbetuximab and for at least 2 hours after the infusion is completed.
(2) Key Observations:
Allergic reactions (urticaria, wheezing, feeling of laryngeal tightness, etc.) and infusion reactions (nausea, vomiting, fever, etc.).
(3) Time Limits
For preparation at room temperature: Complete the infusion within 6 hours;
For preparation under refrigeration: Complete the infusion within 16 hours.
The standardized use of zolbetuximab requires multidisciplinary collaboration. Through accurate dose calculation, strict infusion management, and timely intervention for adverse reactions, clinical use must strictly comply with the product label and the latest clinical guidelines.
