TNT With FLOT/Durvalumab Plus Post-OP Durvalumab for Resectable Gastroesophageal Adenocarcinoma
brief summary
This trial is designed to evaluate a total neoadjuvant approach using D-FLOT as the new standard backbone in patients with resectable esophagogastric adenocarcinoma. It addresses major limitations of current treatment paradigms, builds directly on the strong clinical signal from the MATTERHORN trial, and offers a rational, biologically sound framework for future therapy intensification and innovation. By moving systemic therapy entirely into the preoperative phase, we aim to: * Improve patient outcomes through better adherence and deeper response * Minimize postoperative therapy-related dropout * Create a platform for rational post-surgical drug testing and individualized treatment escalation The trial will provide pivotal evidence to guide the next generation of curative-intent treatment strategies for EGA.
detailed description
The present clinical trial is a prospective, investigator-initiated, single-arm, open-label, multicenter, multi-national phase II trial. Patients with locally advanced, cT2-4 (any cN, M0) or any cT (cN+, M0), gastric, esophagogastric junction (type 1-3) or lower esophageal adenocarcinoma which are considered medically and technically resectable are eligible and will undergo baseline assessment. All patients will receive treatment consisting of up to eight 2-week cycles of FLOT chemotherapy (docetaxel 50 mg/m² IV, oxaliplatin 85 mg/m² IV, folinic acid 200 mg/m² IV, 5-FU 2,600 mg/m² IV; given on day 1 of each 2-weeks cycle \[Q2W\]) in combination with up to four 4-week cycles immunotherapy with durvalumab (1,500 mg IV, given on day 1 of each 4-weeks cycle \[Q4W\]). Four to eight weeks after last dose of preoperative treatment, patients will undergo surgical resection (tailored to the individual patient, according to local standards). Afterwards, patients will enter the maintenance phase receiving durvalumab monotherapy (1,500 mg IV, Q4W) for up to 10 cycles.
official title
Total Neoadjuvant Treatment With Preoperative FLOT/Durvalumab Plus Postoperative Durvalumab for Resectable Gastroesophageal Adenocarcinoma