Zolbetuximab-clzb (Monograph)

Brand name: Vyloy
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

Introduction

Zolbetuximab-clzb, a claudin 18.2-directed cytolytic antibody, is an antineoplastic agent.

Uses for Zolbetuximab-clzb

Zolbetuximab has the following uses:

Zolbetuximab-clzb is indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy 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 adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.

Zolbetuximab-clzb Dosage and Administration

General

Zolbetuximab-clzb is available in the following dosage form(s) and strength(s):

For injection: 100 mg lyophilized powder in a single-dose vial for reconstitution and dilution.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Administer by IV infusion only. Do not administer as an IV push or bolus.
Prior to each infusion, premedicate patients with a combination of antiemetics for the prevention of nausea and vomiting.
The recommended first dose of zolbetuximab-clzb is 800 mg/m² followed by 600 mg/m² every 3 weeks or 400 mg/m² every 2 weeks. To minimize the risk of adverse reactions, begin each infusion at a slower rate for 30 to 60 minutes; if tolerated, gradually increase the rate as described in the prescribing information.
See Full Prescribing Information for additional administration and infusion rate recommendations.

Cautions for Zolbetuximab-clzb

Contraindications

None.

Warnings/Precautions

Hypersensitivity Reactions, Anaphylaxis Reactions, and Infusion Related Reactions

Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when zolbetuximab-clzb has been administered.

Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued zolbetuximab-clzb for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued the drug due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions.

All grade IRRs occurred in 3.2% in patients administered zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received zolbetuximab-clzb. An IRR led to permanent discontinuation of zolbetuximab-clzb in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for zolbetuximab-clzb for 2 (0.4%) patients due to an IRR.

Monitor patients during infusion with zolbetuximab and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension.

If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue zolbetuximab permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the zolbetuximab infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Premedicate the patient with antihistamines for the subsequent infusions, administer per the infusion rates in the prescribing information, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.

Severe Nausea and Vomiting

Zolbetuximab is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment.

All grade nausea and vomiting occurred in 82% and 67%, respectively, of patients treated with zolbetuximab-clzb in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX, respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX.

Nausea led to permanent discontinuation of zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients.

Pretreat with antiemetics prior to each infusion of zolbetuximab. Manage patients during and after infusion with antiemetics or fluid replacement.

Interrupt the infusion, or permanently discontinue zolbetuximab based on severity.

Specific Populations

Pregnancy

There are no data with zolbetuximab use in pregnant women to inform any drug-associated risks. Embryo-fetal toxicity was not observed in pregnant mice intravenously administered zolbetuximab-clzb. Zolbetuximab should only be given to a pregnant woman if the benefit outweighs the potential risk.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.

Lactation

There are no data on the presence of zolbetuximab-clzb in human milk, the effects on the breastfed child, or the effects on milk production. Because antibodies may be excreted in human milk and because of the potential for adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during treatment with zolbetuximab and for 8 months after the last dose.

Females and Males of Reproductive Potential

Zolbetuximab is used in combination with fluoropyrimidine- or platinum-containing chemotherapy. Refer to the Full Prescribing Information of fluoropyrimidine- and platinum-containing chemotherapy products for pregnancy testing, contraception, and infertility information.

Pediatric Use

The safety and effectiveness of zolbetuximab-clzb in pediatric patients have not been established.

Geriatric Use

Of the 533 patients in clinical studies of zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX, 34% (n=179) were over 65 years of age, and 5% were over 75 years of age (n=28). No overall differences in safety or effectiveness were observed between patients 65 years of age or older and younger patients.

Common Adverse Effects

The most common adverse reactions (≥15%) for zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX were nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.

The most common laboratory abnormalities (≥15%) for zolbetuximab-clzb in combination with mFOLFOX6 or CAPOX were decreased neutrophil count, decreased leucocyte 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.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Zolbetuximab-clzb is a claudin 18.2 (CLDN18.2)-directed cytolytic antibody that depletes CLDN18.2-positive cells via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Zolbetuximab in combination with chemotherapy had increased antitumor activity in CLDN18.2-expressing mouse tumor models compared to zolbetuximab-clzb or chemotherapy alone.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).
Advise patients of the risk of hypersensitivity reactions including anaphylaxis and infusion-related reactions and to contact their healthcare provider right away if they experience symptoms of a hypersensitivity or infusion-related reaction during or after the administration of zolbetuximab.
Advise patients of the risk of severe nausea and vomiting and to immediately contact their healthcare provider if they experience persistent or worsening nausea or vomiting.
Advise women not to breastfeed during treatment with zolbetuximab and for 8 months after the last dose of zolbetuximab.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.