Zolbetuximab
FDA Drug Information • Also known as: Vyloy
- Brand Names
- Vyloy
- Dosage Form
- INJECTION
- Product Type
- DRUG FOR FURTHER PROCESSING
Description
11 DESCRIPTION Zolbetuximab-clzb is a chimeric (mouse/human) antibody composed of variable regions derived from mouse anti-human claudin-18 isoform 2 monoclonal antibody and constant regions derived from human IgG1. The molecular weight is approximately 147 kDa. VYLOY (zolbetuximab-clzb) for injection is provided as a sterile, preservative-free, white to off-white lyophilized powder in single-dose vials for intravenous use. VYLOY is supplied as 100 mg or 300 mg per vial and requires reconstitution with Sterile Water for Injection, USP, (5 mL or 15 mL) resulting in a clear to slightly opalescent, colorless to slightly yellow solution with a final concentration of 20 mg/mL . Each mL of reconstituted solution contains 20 mg of zolbetuximab-clzb, arginine (23.24 mg), polysorbate 80 (0.21 mg), sucrose (51.30 mg), and phosphoric acid to adjust pH to 6.0.
What Is Zolbetuximab Used For?
1 INDICATIONS AND USAGE VYLOY, in combination with fluoropyrimidine- and platinum-containing chemotherapy, 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 [see Dosage and Administration ( 2.1 ) and Clinical Studies ( 14 )]. VYLOY 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 ( 1 ).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION
Administer by intravenous infusion only . Do not administer VYLOY as an intravenous push or bolus. ( 2.6 ) The recommended first dose of VYLOY is 800 mg/m 2 followed by 600 mg/m 2 every 3 weeks or 400 mg/m 2 every 2 weeks. ( 2.3 ) 2.1 Patient Selection Select adult patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors are CLDN18.2 positive (defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining) for treatment with VYLOY in combination with fluoropyrimidine- and platinum-containing chemotherapy using an FDA-approved test [see Clinical Studies ( 14 )]. Information on FDA-approved tests for the detection of CLDN18.2 is available at https://www.fda.gov/CompanionDiagnostics . 2.2 Prior to Administration If a patient is experiencing nausea and/or vomiting prior to administration of VYLOY, the symptoms should be resolved to Grade ≤1 before administering the first infusion. Premedication Prior to each infusion of VYLOY, premedicate patients with a combination of antiemetics (e.g., NK-1 receptor blockers and/or 5-HT3 receptor blockers, as well as other drugs as indicated) for the prevention of nausea and vomiting [see Warnings and Precautions ( 5.2 )]. 2.3 Recommended Dosage Administer VYLOY in combination with fluoropyrimidine- and platinum-containing chemotherapy as follows: First dose: 800 mg/m 2 intravenously. Subsequent doses: o 600 mg/m 2 intravenously every 3 weeks, or o 400 mg/m 2 intravenously every 2 weeks. Continue treatment until disease progression or unacceptable toxicity. 2.4 Dosage Modifications for Adverse Reactions No dose reduction for VYLOY is recommended. Adverse reactions for VYLOY are managed by reducing the infusion rate, interruption of the infusion, withholding the dose, and/or permanently discontinuing VYLOY as described in Table 1 . Table 1. Recommended Dose Modifications for VYLOY for Adverse Reactions Adverse Reaction Severity Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0). Dose Modification Hypersensitivity or Infusion-related reactions [see Warnings and Precautions ( 5.1 )]. Grade 2 Interrupt the infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Premedicate and administer the next infusion per the infusion rates in Table 2. Grade 3 Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. or 4 or anaphylaxis Immediately stop the infusion and permanently discontinue. 2.5 Preparation Reconstitution Calculate the recommended dose based on the patient’s body surface area as described in Section 2.3 to determine the total volume and number of vials needed. Reconstitute each vial of VYLOY to achieve a concentration of 20 mg/mL as follows: o 100 mg vial add 5 mL of Sterile Water for Injection. o 300 mg vial add 15 mL of Sterile...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling:
Hypersensitivity Reactions, including anaphylaxis, and infusion related reactions [see Warnings and Precautions ( 5.1 )] . Severe Nausea and Vomiting [see Warnings and Precautions ( 5.2 )] . The most common adverse reactions (≥15%) for VYLOY 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 VYLOY 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, decreased phosphate, decreased potassium, and decreased magnesium ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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/m 2 initial dose followed by subsequent doses of 600 mg/m 2 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, decreased 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/m 2 initial dose followed by 600 mg/m 2 subsequent doses every 3 weeks in combination with mFOLFOX6 [see Clinical Studies ( 14 )] . 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...Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 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.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.