Phase 3 ASP2138 CLDN18.2×CD3 T-cell engager adds to first-line treatment for gastric and GEJ cancer

Astellas Pharma Global Development is running this randomized, double-blind Phase 3 study in locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma. ASP2138 is a CLDN18.2-directed, CD3-binding T-cell engager designed to bring a patient’s T cells into contact with tumor cells. The experimental treatment combines ASP2138 with CAPOX or modified FOLFOX6 chemotherapy and pembrolizumab.

The control receives ASP2138-matching placebo plus chemotherapy, with pembrolizumab or its matching placebo as specified by the protocol. Pembrolizumab is therefore not guaranteed to be part of every control regimen. The study evaluates progression-free and overall survival and the safety of moving T-cell engagement into first-line gastric/GEJ treatment. The clinical rationale differs from that of the approved CLDN18.2 antibody zolbetuximab, which does not redirect T cells through CD3. The trial asks whether this additional T-cell-directed mechanism can improve outcomes enough to justify added treatment complexity and immune toxicity.