The FDA has granted approval to zolbetuximab (Vylov), in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are Claudin 18.2 (CLDN18.2) positive. This approval marks a significant advancement in the treatment landscape for this patient population, addressing a critical unmet need.
The approval is based on data from two phase 3 clinical trials, SPOTLIGHT (NCT03504397) and GLOW (NCT03653507). These trials evaluated the efficacy and safety of zolbetuximab in combination with chemotherapy compared to chemotherapy alone.
SPOTLIGHT Trial
The SPOTLIGHT trial investigated zolbetuximab in combination with mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin). Patients receiving zolbetuximab plus mFOLFOX6 achieved a median progression-free survival (PFS) of 10.6 months (95% CI, 8.9-12.5) compared to 8.7 months (95% CI, 8.2-10.3) in those receiving placebo plus chemotherapy (HR, 0.750; 95% CI, 0.601-0.936; 1-sided P = .0053).
GLOW Trial
The GLOW trial evaluated zolbetuximab in combination with CAPOX (capecitabine and oxaliplatin). The combination generated a median PFS of 8.2 months (95% CI, 7.5-8.8) compared to 6.8 months (95% CI, 6.1-8.1) with placebo plus CAPOX (HR, 0.771; 95% CI, 0.615-0.965; 1-sided P = .0118).
Zolbetuximab is a monoclonal antibody that targets CLDN18.2, a protein expressed in gastric and GEJ adenocarcinomas. By targeting CLDN18.2, zolbetuximab selectively delivers cytotoxic effects to cancer cells, potentially improving treatment outcomes. Prior to initiating treatment with zolbetuximab, patients should undergo assessment for CLDN18.2 expression to determine eligibility.
