OncoMatch/Clinical Trials/NCT07872722

Zolbetuximab, Durvalumab, and FLOT Combination Neoadjuvant Chemotherapy for CLDN18.2-Positive Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Official title: Phase II Trial of Zolbetuximab, Durvalumab, and FLOT (5-FU, Leucovorin, Oxaliplatin, and Docetaxel) Combination Neoadjuvant Chemotherapy for CLDN18.2-Positive Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Is NCT07872722 recruiting? Yes, currently enrolling (Oct 2026). This Phase 2 trial studies multiple treatments including Zolbetuximab and Durvalumab for cldn18.2-positive gastric cancer.

Treatment: Zolbetuximab · Durvalumab · FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) — Claudin 18.2 (CLDN18.2) is a molecular target expressed in a subset of gastric and gastroesophageal junction (GEJ) adenocarcinomas. Zolbetuximab, a chimeric monoclonal antibody targeting CLDN18.2, has shown clinical benefit in combination with chemotherapy for CLDN18.2-positive unresectable advanced or recurrent gastric cancer, and in Japan, FLOT plus durvalumab is expected to become a standard perioperative treatment for locally advanced gastric/GEJ adenocarcinoma. This trial evaluates whether adding zolbetuximab to FLOT plus durvalumab further improves the pathological response of neoadjuvant chemotherapy in CLDN18.2-positive, locally advanced, resectable gastric or GEJ adenocarcinoma. This is a single-arm, open-label, multicenter, investigator-initiated phase II trial conducted at four sites in Japan. Eligible participants are adults (18 years or older) with previously untreated (no prior chemotherapy, radiotherapy, or immunotherapy), histologically confirmed gastric or GEJ adenocarcinoma classified as cT2-4 and/or cN+, M0 by the UICC/TNM Classification (8th edition), confirmed to be CLDN18.2-positive (moderate or greater membranous staining in 75% or more of tumor cells) by immunohistochemistry, with an ECOG performance status of 0 or 1. The primary endpoint is the histological complete response rate (Grade 3) on the surgical specimen, assessed by a central pathological review committee. Key secondary endpoints include the incidence of adverse events, the treatment completion rate through surgery, the dose intensity of neoadjuvant chemotherapy, the R0 resection rate, and the histological response rate (Grade 2 or higher).