Zolbetuximab-clzb
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh, MBBS[2]
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Overview
Zolbetuximab-clzb is a claudin 18.2 (CLDN18.2)-directed cytolytic antibody that is FDA approved for the 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. Common adverse reactions include nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
YLOY is a claudin 18.2-directed cytolytic antibody and 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.
- Administer by intravenous infusion only. Do not administer VYLOY as an intravenous push or bolus.
- The recommended first dose of VYLOY is 800 mg/m2 followed by 600 mg/m2 every 3 weeks or 400 mg/m2 every 2 weeks.
- For injection: 100 mg and 300 mg lyophilized powder in a single-dose vial.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Zolbetuximab-clzb in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Zolbetuximab-clzb in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Zolbetuximab-clzb FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Zolbetuximab-clzb in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Zolbetuximab-clzb in pediatric patients.
Contraindications
None.
Warnings
- Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered.
- Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY 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 VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY 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 VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR.
- Monitor patients during infusion with VYLOY 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 VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY 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 TABLE 2 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
- VYLOY 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 VYLOY 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 VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX.
- Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY 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 VYLOY.
Manage patients during and after infusion with antiemetics or fluid replacement.
- Interrupt the infusion, or permanently discontinue VYLOY based on severity.
Adverse Reactions
Clinical Trials Experience
- Hypersensitivity Reactions, including anaphylaxis, and infusion related reactions.
- Severe Nausea and Vomiting.
Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to VYLOY in 533 patients at an 800 mg/m2 initial dose followed by subsequent doses of 600 mg/m2 every 3 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy in the SPOTLIGHT (279) and GLOW (254) studies. Among 533 patients who received VYLOY in these studies, 47% were exposed for ≥6 months and 20% were exposed for ≥12 months.
- In this pooled population, the most common (≥15%) adverse reactions, were nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia. The most common (≥15%) laboratory abnormalities in the pooled population 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.
SPOTLIGHT
- The safety of VYLOY was evaluated in SPOTLIGHT in patients with locally advanced unresectable or metastatic gastric or GEJ cancer who received at least one dose of VYLOY at an 800 mg/m2 initial dose followed by 600 mg/m2 subsequent doses every 3 weeks in combination with mFOLFOX6.The median duration of exposure to VYLOY in combination with mFOLFOX6 was 6.2 months (range: 1 day to 40.9 months).
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%).
- Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting.
- Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.
Tables 3 and 4 summarize the most common (≥15%) adverse reactions and laboratory abnormalities with a difference between arms of ≥5%, respectively, compared to placebo in SPOTLIGHT.
GLOW
- The safety of VYLOY was evaluated in GLOW in patients with locally advanced unresectable or metastatic gastric/GEJ cancer who received at least one dose of VYLOY at an 800 mg/m2 initial dose followed by 600 mg/m2 subsequent doses every 3 weeks in combination with CAPOX. The median duration of exposure to VYLOY in combination with CAPOX was 4.4 months (range: 0.03 to 30.7 months).
- Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%).
- Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting.
- Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.
Tables 5 and 6 summarize the most common (≥15%) adverse reactions and laboratory abnormalities with a difference between arms of ≥5%, respectively compared to placebo in GLOW.
Postmarketing Experience
There is limited information regarding Zolbetuximab-clzb Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Zolbetuximab-clzb Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Risk Summary
- There are no data with VYLOY use in pregnant women to inform any drug-associated risks. Embryo-fetal toxicity was not observed in pregnant mice intravenously administered zolbetuximab-clzb [see Data]. VYLOY 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.
Data
Animal Data
- In an embryo-fetal development toxicity study, zolbetuximab-clzb was intravenously administered to pregnant mice during the period of organogenesis and did not result in embryo-fetal toxicity at doses up to 300 mg/kg (approximately 1.9 times the recommended clinical dose based on AUC). Zolbetuximab-clzb crossed the placental barrier resulting in higher fetal serum concentrations on Day 18 of gestation than maternal serum concentrations on Day 16 of gestation.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Zolbetuximab-clzb in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Zolbetuximab-clzb during labor and delivery.
Nursing Mothers
Risk Summary
- 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 VYLOY and for 8 months after the last dose.
Pediatric Use
The safety and effectiveness of VYLOY in pediatric patients have not been established.
Geriatic Use
- Of the 533 patients in clinical studies of VYLOY in combination with mFOLFOX6 or CAPOX, 34% (n=179) were over 65 years, and 5% were over 75 years (n=28).
- No overall differences in safety or effectiveness were observed between patients aged 65 years or older and younger patients.
Gender
There is no FDA guidance on the use of Zolbetuximab-clzb with respect to specific gender populations.
Race
There is no FDA guidance on the use of Zolbetuximab-clzb with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Zolbetuximab-clzb in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Zolbetuximab-clzb in patients with hepatic impairment.
Females of Reproductive Potential and Males
VYLOY 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.
Immunocompromised Patients
There is no FDA guidance one the use of Zolbetuximab-clzb in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Zolbetuximab-clzb Administration in the drug label.
Monitoring
There is limited information regarding Zolbetuximab-clzb Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Zolbetuximab-clzb and IV administrations.
Overdosage
There is limited information regarding Zolbetuximab-clzb overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Zolbetuximab-clzb Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Zolbetuximab-clzb Mechanism of Action in the drug label.
Structure
There is limited information regarding Zolbetuximab-clzb Structure in the drug label.
Pharmacodynamics
There is limited information regarding Zolbetuximab-clzb Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Zolbetuximab-clzb Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Zolbetuximab-clzb Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Zolbetuximab-clzb Clinical Studies in the drug label.
How Supplied
There is limited information regarding Zolbetuximab-clzb How Supplied in the drug label.
Storage
There is limited information regarding Zolbetuximab-clzb Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Zolbetuximab-clzb Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Zolbetuximab-clzb interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
VYLOY
Look-Alike Drug Names
There is limited information regarding Zolbetuximab-clzb Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.