La Salle

Researchers are evaluating the safety, tolerability, pharmacokinetics, and early anti-tumor activity of new drugs or combinations given before and after surgery in adults with locally advanced resectable gastric, gastroesophageal junction GEJ, or esophageal adenocarcinoma who have not had prior treatment for this disease. This Phase II, open-label study includes multiple sub-studies to test different novel drug combinations in participants. Participants will be assigned to one of three sub-studies where they receive combinations of investigational drugs such as AZD0901, Rilvegostomig, Trastuzumab Deruxtecan T-DXd, and chemotherapy agents like 5-Fluorouracil 5-FU, Capecitabine, or FLOT chemotherapy. Treatment is given as neoadjuvant before surgery and adjuvant after surgery therapy, with Rilvegostomig continuing as monotherapy after these phases. Drugs are administered mainly by intravenous infusion, except for Capecitabine, which is given orally. Participants will be closely monitored throughout the study for side effects and response to treatment, including assessments of surgical success, tumor response, event-free survival, and overall survival up to 38 months. Regular evaluations include clinical exams, laboratory tests, and pharmacokinetic measurements to track drug levels and immune response. The study aims to gather comprehensive safety and effectiveness data during the treatment and follow-up periods.