Zolbetuximab (brand name: VYLOY) is a cytolytic antibody targeting Claudin 18.2 (CLDN18.2). It was first approved for marketing in the United States in 2024. It is indicated for the first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma, and the tumor must be confirmed as CLDN18.2-positive (≥75% of tumor cells showing moderate to strong membranous staining) through an FDA-approved test.

Zolbetuximab: Clinical Uses, Recommended Dosage, Potential Side Effects

I. Medication Guide

1. Target Population and Testing Requirements

(1) Indications

Adult patients with CLDN18.2-positive (confirmed by an FDA-approved test) and HER2-negative gastric/gastroesophageal junction adenocarcinoma.

(2) Contraindications

There are no absolute contraindications, but permanent discontinuation of the drug is required in case of severe allergic reactions or infusion reactions.

2. Administration Regimen

(1) Dosage

The initial dose of Zolbetuximab is 800 mg/m², followed by subsequent doses of 600 mg/m² every 3 weeks or 400 mg/m² every 2 weeks, until disease progression or intolerable toxicity occurs.

(2) Administration Method

a. For intravenous infusion only; intravenous push or rapid injection is prohibited.

b. Reconstitute with sterile water for injection (100 mg/5 mL or 300 mg/15 mL), then dilute in 0.9% sodium chloride solution to a final concentration of 5 mg/mL.

c. Antiemetic drugs (e.g., NK-1/5-HT3 receptor antagonists) must be taken before infusion.

3. Infusion Management

(1) Infusion Rate

For the first dose: The initial rate is 100 mg/m²/hour; if well-tolerated, the rate can be increased to 200-265 mg/m²/hour.

For subsequent doses: Adjust the rate according to the administration regimen.

(2) Precautions

a. Monitor for allergic reactions for at least 2 hours during and after the infusion.

b. When administered on the same day as chemotherapy, Zolbetuximab must be infused first.

II. Adverse Reactions and Management

1. Common Adverse Reactions (≥15%)

(1) Gastrointestinal Reactions

Nausea (82%), vomiting (67%), diarrhea, constipation, abdominal pain.

(2) Systemic Reactions

Fatigue, fever, decreased appetite, weight loss.

(3) Hematological Abnormalities

Neutropenia, anemia, thrombocytopenia.

(4) Metabolic Disorders

Hypoproteinemia, hypokalemia/hypnatremia/hypomagnesemia.

2. Severe Adverse Reactions

(1) Allergic and Infusion Reactions (Incidence: 18%)

Including anaphylactic shock (0.4% fatal), laryngeal edema, etc. Immediate discontinuation of the drug and emergency treatment are required.

(2) Severe Nausea and Vomiting (16% are Grade 3)

It is more common in the first treatment cycle; an enhanced antiemetic regimen (e.g., dexamethasone combined with antiemetics) is required.

3. Dosage Adjustment

(1) Allergic/Infusion Reactions

a. Grade 2: Pause the infusion; resume at a reduced rate after symptoms subside.

b. Grade 3-4: Discontinue the drug permanently.

(2) Nausea and Vomiting

Grade 3: Pause administration until symptoms subside.

Grade 4: Discontinue the drug permanently.

III. Precautions for Special Populations

1. Pregnancy and Lactation

(1) Pregnancy

Animal studies have not shown embryonic toxicity, but human data are insufficient; the benefits and risks must be weighed before use.

(2) Lactation

Breastfeeding is prohibited during treatment and within 8 months after the last dose.

2. Hepatic and Renal Impairment

For patients with mild to moderate renal impairment or mild hepatic impairment, no dosage adjustment of Zolbetuximab is required.

The safety of Zolbetuximab in patients with severe hepatic or renal impairment has not been fully confirmed and requires further clinical observation.

3. Elderly Patients

In elderly patients aged ≥65 years (accounting for 34% of clinical trial participants), there is no significant difference in the safety and efficacy of Zolbetuximab compared with younger populations.

IV. Patient Information

1. Recognition of Allergic Reactions

Seek medical attention immediately if severe symptoms such as urticaria, obvious difficulty in breathing, or a feeling of laryngeal constriction occur.

2. Management of Nausea and Vomiting

Take antiemetic drugs strictly as prescribed by the doctor; report to the doctor if symptoms continue to worsen.

3. Follow-up Monitoring

Regularly undergo tests for blood routine, electrolytes, liver function, and renal function.

Zolbetuximab provides a new treatment option for patients with CLDN18.2-positive gastric cancer, but its use must strictly comply with the standards for test screening and adverse reaction management.