Zolbetuximab

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. 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.

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-clzb in combination with chemotherapy had increased antitumor activity in CLDN18.2-expressing mouse tumor models compared to zolbetuximab-clzb or chemotherapy alone.

• Administer by intravenous infusion only. Do not administer VYLOY as an intravenous push or bolus. • 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.

None. None.

• Hypersensitivity reactions including serious anaphylaxis reactions and serious and fatal infusion-related reactions have occurred. Monitor patients during and for at least 2 hours after infusion with VYLOY. Interrupt, slow the rate of infusion or permanently discontinue VYLOY based on severity and type of reaction. Premedicate with antihistamines for subsequent infusions after a hypersensitivity reaction. • Severe nausea and vomiting: Premedicate patients with antiemetics prior to each infusion. Interrupt or permanently discontinue VYLOY based on the severity of the nausea and/or vomiting. Manage patients during and after infusion with antiemetics or fluid replacement.

The following serious adverse reactions are described elsewhere in the labeling: • Hypersensitivity Reactions, including anaphylaxis, and infusion related reactions. • Severe Nausea and Vomiting. 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.