Multinational phase 2 trial of first-line zolbetuximab plus mFOLFOX6 and nivolumab for unresectable CLDN18.2-positive G/GEJ adenocarcinoma

Cohort 4 of the multinational phase 2 ILLUSTRO trial evaluated first-line zolbetuximab (CLDN18.2 targeting antibody) plus mFOLFOX6 and nivolumab (anti-PD-L1) for unresectable CLDN18.2-positive, HER2-negative metastatic gastric/gastroesophageal junction (mG/GEJ) adenocarcinoma. The safety lead-in phase cohort 4A included 12 patients, after which cohort 4B enrolled 71 patients who were treated with zolbetuximab 800 mg/m² once every 3 weeks. Among the 77 patients receiving this dose, 85.5% had CLDN18.2-high tumors. Cohort 4B median follow-up was 11.5 months. The median progression-free survival was 14.8 months (95% CI 14.8-NE) overall and 18.0 months (11.1-NE) in patients with CLDN18.2-high tumors (n=59). Objective response rate in patients with measurable disease was 62.1% (95%CI 48.4-74.5) in 4B overall (n=58) and 68.1% in CLDN18.2-high (n=47). The most common treatment-emergent adverse events were nausea (80.5%) and decreased appetite (72.7%). The authors conclude that these results support randomized evaluation of zolbetuximab plus chemoimmunotherapy in patients with CLDN18.2-positive and PD-L1-positive mG/GEJ adenocarcinoma.