Adaptive Treatment Using Biomarkers to Guide Chemotherapy, Immunotherapy, and Targeted Therapy in Stomach and Esophageal Adenocarcinoma

What this Trial Is About

Researchers are evaluating a new personalized treatment approach for patients with stomach or esophageal adenocarcinoma. This two-stage study aims to find the best combination of chemotherapy, immunotherapy, and targeted drugs based on each patients tumor biomarkers. The study considers tumor biomarker testing to guide treatment decisions and assesses whether some patients can safely avoid surgery depending on their response. Participants receive treatments including chemotherapy drugs mFOLFOX6, immune checkpoint inhibitors tislelizumab, and targeted therapies zanidatamab or zolbetuximab depending on their biomarker status. Stage I involves about four months of preoperative therapy followed by surgery and then up to eight months of postoperative therapy, totaling one year. Stage II focuses on patients whose treatments showed sufficient efficacy in Stage I, providing the same combination therapy for four months, with surgery potentially skipped if there is no residual disease. Those skipping surgery continue maintenance therapy and are closely monitored. Throughout the study, participants undergo tumor biopsies and biomarker testing, clinical, endoscopic, and radiologic evaluations to assess treatment response. Monitoring includes regular scans and endoscopies, especially for those avoiding surgery. Researchers measure outcomes such as pathological complete response rates at surgery and organ preservation rates up to 12 months after treatment. Safety and tolerability are tracked during treatment and up to 30 days post-treatment, with long-term follow-up assessing survival and correlations with circulating tumor DNA. Participation lasts up to one year with extended follow-up for some outcomes.

AACR Adaptive Biomarker-Driven Organ Preservation Trial in Gastroesophageal Adenocarcinomas