Vyloy Drug Information

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.

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. Information on FDA-approved tests for the detection of CLDN18.2 is available at https://www.fda.gov/CompanionDiagnostics.

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.

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.

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

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 Water for Injection. • Slowly add the Sterile Water for Injection into the VYLOY vial, and direct the stream toward the inside wall of the vial. Do not inject directly onto the lyophilized powder. • Slowly swirl each vial until the contents are completely dissolved. Allow the reconstituted vial(s) to settle until the bubbles are gone.

Do not shake the vial. • Visually inspect the reconstituted solution for particulate matter and discoloration. The reconstituted solution should be clear to slightly opalescent, colorless to slight yellow and free of visible particles. Discard any vial with visible particles or discoloration. • Store reconstituted vial(s) at room temperature 15°C to 30°C (59°F to 86°F) for up to 5 hours if not used immediately.

This product does not contain a preservative. Dilution • Withdraw the required volume of reconstituted VYLOY vial(s) and transfer into an infusion bag containing 0.9% Sodium Chloride Injection, to a final concentration of 5 mg/mL. o The diluted solution of VYLOY is compatible with intravenous infusion bags composed of polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), ethylene propylene copolymer, ethylene-vinyl acetate (EVA) copolymer, PP and styrene-ethylene-butylene-styrene copolymer. o The diluted solution of VYLOY is compatible with infusion tubing composed of PE, PVC, polybutadiene (PB), or elastomer modified polypropylene with in-line filter membranes composed of polyethersulfone (PES) or polysulfone. • Mix diluted solution by gentle inversion. Do not shake the bag. • Visually inspect the infusion bag for any particulate matter prior to use.

The diluted solution should be free of visible particles. Do not use the infusion bag if particulate matter is observed. • Discard any unused portion left in the single-dose vials. Storage of diluted infusion • Store the prepared infusion bag: o At room temperature 15°C to 30°C (59°F to 86°F) for no longer than 6 hours from the end of the preparation of the infusion bag to the completion of the infusion. o Under refrigeration at 2°C to 8°C (36°F to 46°F) for no longer than 16 hours from the end of the preparation of the infusion bag to the completion of the infusion.

Do not freeze.

Administration • Administer

VYLOY as an intravenous infusion only. Do NOT administer as an intravenous push or bolus. • If VYLOY and fluoropyrimidine- and platinum-containing chemotherapy are administered on the same day, VYLOY must be administered first. • No incompatibilities have been observed with o closed system transfer devices composed of PP, PE, stainless steel, silicone (rubber/oil/resin), polyisoprene, PVC with TOTM plasticizer, acrylonitrile-butadiene-styrene (ABS) copolymer, methyl methacrylate-ABS copolymer, thermoplastic elastomer, polytetrafluoroethylene, polycarbonate, PES, acrylic copolymer, polybutylene terephthalate, PB, or EVA copolymer. o central ports composed of silicone rubber, titanium alloy or PVC with TOTM plasticizer. • In-line filters (pore size of 0.2 μm composed of materials listed above) are recommended to be used during administration. • Do NOT co-administer other drugs through the same infusion line. • Immediately administer the infusion as described in Table 2. 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 Table 2. • If the infusion time exceeds the recommended storage time (6 hours from end of preparation of infusion solution at room temperature or 16 hours from end of preparation of infusion solution under refrigeration), the infusion bag must be discarded and a new infusion bag prepared to continue the infusion.

Infusion Rate Recommendations Table 2. Infusion Rates Recommended f

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. 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. The median duration of exposure to VYLOY in combination with mFOLFOX6 was 6.2 months (range: 1 day to 40.9 months). 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. Table 3. The median duration of exposure to VYLOY in combination with CAPOX was 4.4 months (range: 0.03 to 30.7 months).

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. Table 5. Adverse Reactions (≥15%) in Patients Treated with VYLOY in GLOW with a Difference Between Arms of ≥5% Compared to Placebo Other clinically relevant adverse reactions (<15%) in GLOW with a difference between arms of 5% compared to placebo included peripheral edema.

Table 6. Laboratory Abnormalities (≥15%) in Patients Treated with VYLOY in GLOW with a Difference Between Arms of ≥5% Compared to Placebo 0

Post-Marketing Experience

The following adverse reactions have been identified during post approval use of VYLOY. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal Disorders: gastritis, protein-losing gastroenteropathy

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. 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. 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.

Pediatric Use The safety and effectiveness of VYLOY in pediatric patients have not been established.