Tokyo, Japan, August 25, 2026
Astellas Pharma Inc. announced that the first patient has been dosed in a Phase 3 study of ASP2138 for adults with CLDN18.2-positive and HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The investigational therapy is being evaluated in combination with chemotherapy and pembrolizumab as a first-line treatment, marking the program’s advancement into late-stage clinical development. The randomized Phase 3 study is designed to evaluate whether ASP2138 can improve outcomes in this biomarker-defined patient population, where treatment options remain an area of significant unmet need. Astellas said the advancement strengthens its broader commitment to CLDN18.2-targeted cancer research, with a portfolio spanning approved treatments and investigational medicines. The study is planned to enroll approximately 570 participants across multiple countries, with overall survival and progression-free survival serving as co-primary endpoints.
ASP2138 Targets CLDN18.2 and CD3-Positive T Cells
ASP2138 is an investigational subcutaneous bispecific antibody designed to target CLDN18.2 and CD3-positive T cells. CLDN18.2 is a tight-junction protein normally found in gastric mucosal cells that can remain present on certain gastric and GEJ cancer cells, making it an increasingly important target for cancer drug development. ASP2138 is designed to bind CLDN18.2 on tumor cells while simultaneously engaging CD3-positive T cells. This mechanism is intended to bring immune cells into close proximity with CLDN18.2-expressing cancer cells and activate an anti-tumor immune response. The Phase 3 program will provide important clinical evidence on whether this approach can translate into improved outcomes when combined with established first-line treatment strategies. Astellas emphasized that the safety and efficacy of ASP2138 have not yet been established for the investigated use.
Phase 3 Study Evaluates Survival and Disease Control
The randomized, double-blind, placebo-controlled Phase 3 trial will compare ASP2138 plus chemotherapy and pembrolizumab against a placebo-based control regimen involving chemotherapy with or without pembrolizumab. Participants will receive either CAPOX or mFOLFOX6 chemotherapy, reflecting commonly used treatment backbones in advanced gastric and GEJ cancer. The study’s co-primary endpoints are overall survival (OS) and progression-free survival (PFS), allowing investigators to assess both long-term survival and the time patients remain alive without disease progression. The trial is specifically enrolling patients whose tumors are CLDN18.2-positive and HER2-negative, making biomarker testing an important component of patient selection. With approximately 570 participants expected to participate across multiple countries, the study is intended to generate pivotal evidence capable of supporting future regulatory discussions if the results demonstrate a favorable benefit-risk profile.
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Astellas Expands Late-Stage CLDN18.2 Strategy
The first-patient dosing milestone makes ASP2138 a key late-stage program within Astellas’ immuno-oncology strategy and supports the company’s broader objective of advancing multiple innovative approaches against CLDN18.2-positive cancers. Astellas is exploring different scientific modalities and mechanisms to better understand how CLDN18.2-targeted therapies could address varying patient needs in gastric and GEJ cancers. The company said ASP2138’s progression to Phase 3 also contributes to its Corporate Strategic Plan ambition of initiating five or more Phase 3 or pivotal studies by fiscal year 2027. For patients with advanced gastric and GEJ adenocarcinoma, the development is particularly relevant because outcomes remain challenging despite recent treatment advances. However, ASP2138 remains investigational, and successful Phase 3 results and regulatory approval will be required before it can become an available treatment option.
Source:Astellas Pharma press relese
