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Zolbetuximab, Durvalumab, and FLOT Combination Neoadjuvant Chemotherapy for CLDN18.2-Positive Gastric Cancer or Gastroesophageal Junction Adenocarcinoma
Sponsor: National Cancer Center, Japan
Summary
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).
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
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
29
Start Date
2026-08-13
Completion Date
2030-03-31
Last Updated
2026-10-14
Healthy Volunteers
No
Conditions
Interventions
Zolbetuximab
Zolbetuximab 800 mg/m\^2 (loading dose; reduced to 600 mg/m\^2 if not tolerated) is administered intravenously on Cycle 1 Day 1, followed by 400 mg/m\^2 on Day 1 of Cycles 2-4 (2-week cycles).
Durvalumab
Durvalumab 1,500 mg (or 20 mg/kg for participants weighing 30 kg or less) is administered intravenously on Cycle 1 Day 2 and Cycle 3 Day 1 or 2 only (2 administrations in total).
FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel)
FLOT (5-fluorouracil 2,600 mg/m\^2, leucovorin 100 mg/m\^2, oxaliplatin 85 mg/m\^2, and docetaxel 50 mg/m\^2) is administered intravenously every 2 weeks for 4 cycles, in combination with zolbetuximab and durvalumab, as neoadjuvant treatment prior to surgery.
Locations (4)
Saitama Cancer Center
Saitama, Japan
National Cancer Center Hospital
Tokyo, Japan
The Cancer Institute Hospital of JFCR
Tokyo, Japan
Kanagawa Cancer Center
Yokohama, Japan