Instructions for Vyloy (zolbetuximab-clzb)

1. Name:Vyloy, zolbetuximab-clzb, zotuximab (transliteration), IMAB362

2. Indications:

Vyloy (zolbetuximab-clzb), in combination with a fluoropyrimidine- and platinum-containing chemotherapy regimen, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2-positive as determined by an FDA-approved test.

3. Usage and dosage:

1. Patient Selection: Select adult patients with locally advanced unresectable or metastatic HER2-negative gastric adenocarcinoma or GEJ adenocarcinoma whose tumors are CLDN18.2-positive (defined as ≥75% of tumor cells showing moderate to strong membrane CLDN18 immunohistochemical staining) for treatment with Vyloy in combination with fluoropyrimidine and platinum-containing chemotherapy using an FDA-approved test.

2. Before use: If the patient experiences nausea and/or vomiting before using Vyloy, the symptoms should be alleviated to ≤ grade 1 before the first infusion. Before each infusion of Vyloy, patients should be premedicated with antiemetics (such as NK-1 receptor blockers and/or 5-HT3 receptor blockers, and other prescribed medications) to prevent nausea and vomiting.

3. Recommended dose: The combination of Vyloy and chemotherapy containing fluoropyrimidine and platinum is as follows: the first intravenous injection dose is 800mg/m2 (mg/m2); subsequent intravenous injection dose is 600mg/m2 intravenously every 3 weeks, or 400mg/m2 every 2 weeks, and treatment continues until the disease worsens or unacceptable toxicity occurs. If VYLOY and fluoropyrimidine- and platinum-containing chemotherapy are given on the same day, Vyloy must be given first.

4. Dose adjustment: It is not recommended to reduce the dose of Vyloy.

4. Adverse reactions:

In clinical studies of Vyloy, the most common (≥15%) adverse reactions were nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, weight loss, hypersensitivity reactions, and pyrexia; the most common (≥15%) laboratory abnormalities were Decreased neutrophil count, decreased white blood cell count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, increased phosphate, decreased potassium, and decreased magnesium.

5. Supply and storage:

Vyloy for injection is a sterile, preservative-free white to off-white lyophilized powder packaged in single-dose vials, each containing 100 mg of Vyloy. Store Vyloy vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton. Do not freeze. Don't shake.

6. Special groups:

1. Breastfeeding women: There are no data on the presence of zolbetuximab-clzb in breast milk, the effects on breastfed children, or the effects on milk production. Because antibodies may be secreted in breast milk and adverse reactions may occur in breastfed children, lactating women are advised not to breastfeed during treatment with Vyloy and for 8 months after the last dose.

7. Mechanism of action:

zolbetuximab-clzb is a tight junction protein 18.2 (CLDN18.2)-directed cytolytic antibody that depletes CLDN18.2-positive cells via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Compared with zolbetuximab-clzb or chemotherapy alone, zolbetuximab-clzb combination chemotherapy had enhanced antitumor activity in a mouse tumor model expressing CLDN18.2.

8. Pharmacodynamics and Pharmacokinetics

Exposure-response relationships for the efficacy and safety of zolbutuximab-clzb at recommended doses have not been fully established in patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are CLDN18.2-positive. After 2 hours of intravenous infusion, zolbetuximab-clzb exhibited dose-proportional pharmacokinetics (0.04 times to 1.25 times the recommended initial dose) over the dose range of 33 mg/m2 to 1000 mg/m2. When the first dose was 800 mg/m2, followed by 600 mg/m2 every 3 weeks, a steady state was reached at week 18 with a geometric mean (coefficient of variation [CV]%) Cmax of 415 (22%) mcg/mL and an AUCtau of 3149 (37%) days*mcg/mL.

8. Notes:

In clinical studies of Vyloy, cautions including allergic reactions, including anaphylaxis and infusion-related reactions, severe nausea and vomiting, have occurred.