FDA Approval Insights: Zolbetuximab for CLDN18.2+ HER2-Negative Gastric and GEJ Adenocarcinoma

Season 11, Episode 35,   Nov 14, 11:05 PM

In this episode, Dr. Ajani discussed key considerations for the clinical use of zolbetuximab, including its anticipated adverse effect profile and the introduction of CLDN18.2 as a biomarker for assessment prior to treatment initiation.

On October 18, 2024, the FDA approved zolbetuximab plus fluoropyrimidine- and platinum-containing chemotherapy for the frontline treatment of adult patients with locally advanced unresectable or metastatic, HER2-negative, CLDN18.2-positive gastric or GEJ adenocarcinoma. This regulatory decision was backed by findings from the phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) trials. In SPOTLIGHT, In SPOTLIGHT, patients who received zolbetuximab plus mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin) achieved a median progression-free survival (PFS) of 10.6 months (95% CI, 8.9-12.5) vs 8.7 months (95% CI, 8.2-10.3) in those who received placebo plus chemotherapy (HR, 0.750; 95% CI, 0.601-0.936; 1-sided P = .0053). In GLOW, zolbetuximab plus CAPOX (capecitabine and oxaliplatin) generated a median PFS of 8.2 months (95% CI, 7.5-8.8) vs 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).


In our exclusive interview, Dr Ajani discussed key considerations for the clinical use of zolbetuximab, including its anticipated adverse effect profile and the introduction of CLDN18.2 as a biomarker for assessment prior to treatment initiation.