Gastric Adenocarcinoma

P2, N=100, Recruiting, Jeeyun Lee | N=50 --> 100

P2, N=2, Active, not recruiting, National Cancer Institute (NCI) | N=240 --> 2 | Trial completion date: Oct 2027 --> Jun 2027 | Trial primary completion date: Oct 2027 --> Jan 2026

The anti-Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) monoclonal antibody ramucirumab was the first antiangiogenic agent approved for HER2-negative metastatic gastric adenocarcinomas and remains a standard second-line treatment either alone or in combination with paclitaxel. Other VEGFR-targeting agents, such as the tyrosine kinase inhibitors (TKI) regorafenib and apatinib, have failed to demonstrate any survival benefit in the first-line settings, while providing modest improvements in pretreated patients, even when combined with Immune Checkpoint Inhibitors (ICI)...Although several biomarker candidates have been explored, reliable predictors are still awaited. This review summarizes current evidence and explores the future of antiangiogenic agents in gastric cancers.

P3, N=332, Not yet recruiting, Peking University

P1/2, N=186, Recruiting, Zhejiang Doer Biologics Co., Ltd. | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Apr 2026 --> Apr 2027

In the RATIONALE-305 trial, first-line tislelizumab + chemotherapy (CAPOX ([capecitabine + oxaliplatin] or 5-fluorouracil [5-FU] + cisplatin) significantly improved overall and progression-free survival (PFS) versus placebo + chemotherapy in unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC). This exploratory analysis evaluated the comparative efficacy of tislelizumab + CAPOX versus tislelizumab + CAPOX or FOLFOX (5-FU, leucovorin, oxaliplatin) using a matching-adjusted indirect comparison (MAIC) approach...Although median PFS was numerically longer with the mixed chemotherapy backbone, these findings are exploratory in nature and warrant further investigation. ClinicalTrials.gov, RATIONALE-305 (NCT03777657); DisTinGuish (NCT04363801).

NOX4 emerges as a key regulator of the STAD inflammatory microenvironment and a robust prognostic biomarker. Its role in immune modulation and chemoresistance provides novel insights for developing precision therapeutic strategies in STAD.

Based on multi-omics integration, this study establishes PRGs signature as a robust prognostic biomarker for STAD, enabling risk stratification, molecular subtyping, and prediction of immunotherapy response while elucidating PRGs-mediated remodeling of the tumor-immune microenvironment. The online version contains supplementary material available at 10.1007/s10616-026-01014-7.

P3, N=600, Recruiting, NingBo Junyan Hongshi Biosciences Co., Ltd | Not yet recruiting --> Recruiting

P3, N=570, Not yet recruiting, Astellas Pharma Global Development, Inc.

P1, N=15, Active, not recruiting, Mayo Clinic | Trial completion date: Apr 2030 --> Jun 2029 | Recruiting --> Active, not recruiting

Zolbetuximab, a CLDN18.2-targeted monoclonal antibody, has been approved in combination with chemotherapy as a first-line treatment option for patients with HER2-negative and CLDN18.2-positive gastric adenocarcinoma...In conclusion, precision targeting of CLDN18.2 represents a promising approach in GC therapy, shifting from conventional chemotherapy to biomarker-guided strategies. Continued development of next-generation agents and rational combination therapies may enhance outcomes and expand benefit.