Zolbetuximab has demonstrated significant therapeutic potential in the treatment of malignant tumors such as gastric cancer. Currently, zolbetuximab has not yet been launched in China. This article provides a detailed explanation of zolbetuximab, including its indications, dosage and administration, side effects, contraindications, and clinical efficacy.

Instructions for zolbetuximab

(I) Indications

Zolbetuximab is indicated for the treatment of unresectable, advanced, and recurrent gastric cancer positive for Claudin 18.2 (CLDN18.2).

(II) Dosage and Administration

1. Recommended Dosage

(1) When used in combination with other antineoplastic therapeutic drugs, the recommended initial dose of zolbetuximab for adult patients is 800 mg/m². For the second and subsequent doses, the dosage can be reduced to 600 mg/m², and after an interval of 3 weeks, it can be further reduced to 400 mg/m². The drug is administered via intravenous infusion over a period of more than 2 hours, with an interval of every 2 weeks.

(2) When using zolbetuximab in combination with other antineoplastic drugs, one should be familiar with the relevant clinical manifestation information. For specific details, please consult professionals or refer to the package insert.

2. Infusion Rate

For patients who tolerate zolbetuximab well, the infusion rate can be gradually increased 30-60 minutes after the start of administration. However, the specific rate should be in accordance with the guidance of a professional doctor.

3. Dosage Adjustment

Patients may experience adverse reactions during the use of zolbetuximab. When adverse reactions occur, the dosage of the drug can be adjusted.

(III) Target Population

Adults. Pregnant women, lactating women, children, and elderly patients should use this drug under the guidance of a doctor.

(IV) Contraindications

Patients with a severe allergic history to the components of zolbetuximab are contraindicated from using this drug.

(V) Side Effects

Common side effects include allergic reactions, and severe nausea or vomiting.

Other adverse reactions include neutropenia, anemia, thrombocytopenia, leukopenia, decreased appetite, hypoalbuminemia, hypertension, abdominal pain, constipation, diarrhea, fatigue, asthenia, lassitude, fever, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), and weight loss. For more adverse reactions, please refer to the drug package insert.

(VI) Precautions

1. Precautions for Pharmaceutical Preparation

(1) Reconstitution

Zolbetuximab needs to be reconstituted with 5.0 mL of water for injection specified in the Japanese Pharmacopoeia, resulting in a drug concentration of 20 mg/mL after reconstitution. Aseptic conditions must be maintained during reconstitution: the water for injection should be slowly injected along the inner wall of the zolbetuximab vial. Shaking is not allowed; instead, the solution should be gently stirred until it is completely dissolved.

After reconstitution, the solution must be allowed to stand to let air bubbles in the vial disappear. Direct sunlight exposure should be avoided throughout the entire preparation process. The reconstituted solution should be a clear liquid ranging from colorless to slightly yellow.

(2) Dilution

Draw the required volume of the reconstituted solution from the vial and add it to an intravenous infusion bag containing normal saline, adjusting the diluted concentration to 2.0 mg/mL. Gently invert the infusion bag to mix the solution (to avoid foaming), and ensure no direct sunlight exposure throughout the process. Visually inspect the diluted solution for the presence of particles; if particles are found, the solution must not be used.

The diluted drug should be used promptly. Under room temperature, the diluted drug must be administered within 6 hours. If storage of the diluted drug is necessary, it should be stored at 2-8°C and used as soon as possible within 24 hours after dilution. Any unused residual solution should be discarded promptly. Do not use the same infusion line for concurrent administration with other drugs.

(VII) Therapeutic Efficacy

1. Study Design

This is a randomized Phase II study comparing zolbetuximab (IMAB362) combined with EOX (epirubicin, oxaliplatin, capecitabine) versus EOX alone as first-line treatment for advanced CLDN18.2-positive gastric cancer and gastroesophageal junction adenocarcinoma.

2. Study Outcome Settings

The FAST study enrolled patients with advanced gastric/gastroesophageal junction and esophageal adenocarcinoma (aged ≥18 years) whose tumors showed moderate to strong expression of CLDN18.2 in ≥40% of tumor cells. Patients received first-line treatment with epirubicin + oxaliplatin + capecitabine (EOX, Group 1, n=84) every 3 weeks (Q3W), or zolbetuximab + EOX (loading dose: 800 mg/m², followed by 600 mg/m² Q3W) (Group 2, n=77). Group 3 (exploratory) was added after the start of enrollment (zolbetuximab + EOX 1000 mg/m² Q3W, n=85). The primary endpoint was progression-free survival (PFS), and overall survival (OS) was a secondary endpoint.

3. Study Results

In patients with advanced gastric/gastroesophageal junction and esophageal adenocarcinoma expressing CLDN18.2, the addition of zolbetuximab to first-line EOX prolonged PFS and OS compared with EOX alone. Zolbetuximab + EOX was generally well-tolerated, and adverse reactions were manageable.

(VIII) Drug Interactions

Not yet determined.

(IX) Storage Conditions

Store at 2-8°C.

【Kind Reminder】: The package inserts of some products are updated frequently. Please refer to the actual product for the most accurate information.