Phase 2 Study Comparing Trastuzumab Deruxtecan Plus Fluoropyrimidine to Standard Chemotherapy After Surgery in HER2-Positive Gastric or Gastroesophageal Cancer Patients with Minimal Residual Disease Detected by Liquid Biopsy

What this Trial Is About

Researchers are evaluating the activity, efficacy, and safety of trastuzumab-deruxtecan T-DXd combined with capecitabine or 5-fluorouracil as a post-operative treatment in patients with localized or locally advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma cancers that overexpress or amplify HER2. This phase II multicenter, randomized, open-label study targets patients who have positive circulating tumor DNA ctDNA after pre-operative chemotherapy with FLOT 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel followed by radical surgery. The study aims to improve understanding of treatment effects in this specific patient group identified by minimal residual disease detected by liquid biopsy. The trial includes an observational phase where patients receive standard pre-operative FLOT chemotherapy and surgery while undergoing multiple liquid biopsies to detect ctDNA. Eligible patients with positive post-operative ctDNA are randomized to receive either the experimental treatment of T-DXd at 6.4 mgkg intravenously every 3 weeks combined with either capecitabine orally or 5-fluorouracil infusion for six cycles, or the control arm receiving post-operative FLOT chemotherapy for four cycles. The study includes pre-screening, screening, treatment, and follow-up phases with scheduled CT scans and echocardiography. Participants will have several assessments including blood samples for ctDNA at baseline, end of pre-operative treatment, post-surgery, and at multiple time points after randomization. Imaging scans occur every three months for one year to monitor for disease relapse. The primary outcome is ctDNA clearance measured at one year post-randomization. Secondary outcomes include disease-free survival, overall survival, metastases-free survival, quality of life during treatment, and safety over six months. The total participation may extend up to three years with continued follow-up and monitoring.

Adjuvant TRastuzumab Deruxtecan for HER2-positive Gastroesophageal Cancer With Persistence of miNImal Residual Disease