NCT07053332

A Study on Immunotherapy Combined With Radiotherapy for Esophagogastric Junction/Gastric Adenocarcinoma

A Single-arm, Prospective Phase II Clinical Study of Neoadjuvant PD-1/CTLA-4 Combination Antibody With Low-dose Radiotherapy in Resectable dMMR/MSI-H Esophagogastric Junction/Gastric Adenocarcinoma.

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Jiangsu Cancer Institute & Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

A single-arm, prospective phase II clinical study of neoadjuvant PD-1/CTLA-4 combination antibody with low-dose radiotherapy in resectable dMMR/MSI-H esophagogastric junction/gastric adenocarcinoma.

Detailed description

This study is a prospective, single-center, single-arm Phase II clinical trial. Participants will be patients with resectable locally advanced dMMR/MSI-H esophagogastric junction/gastric adenocarcinoma staged as cT1-2N1-3M0 or T3-T4aN0-3M0 according to the AJCC/UICC staging system. The objective of this study is to evaluate the safety and efficacy of PD-1/CTLA-4 combination antibody therapy combined with low-dose radiotherapy in patients with locally advanced resectable dMMR/MSI-H esophagogastric junction/gastric adenocarcinoma. Eligible participants who meet the inclusion criteria will be enrolled in the study. Primary endpoint: Pathological complete response rate (pCR), defined as pT0N0M0，Safety: Treatment-related adverse reactions of grade 3 or above according to CTCAE 5.0 will be recorded from the start of treatment until 30 days after surgery.. Secondary endpoints: Treatment feasibility: the proportion of patients who complete neoadjuvant therapy and undergo surgery within 3-5 weeks after treatment. Major pathological response rate (MPR): the percentage of residual viable tumor cells in the tumor bed after neoadjuvant therapy ≤10%. Imaging-assessed response rate: evaluated using multimodal imaging including CT/GI ultrasound and MRI. R0 resection rate: the proportion of patients achieving R0 resection among all enrolled patients. Treatment safety: recorded using CTCAE 5.0 for grade 3 or higher treatment-related adverse events, from the start of neoadjuvant therapy until 30 days after surgery. Postoperative complications: assessed using the Clavien-Dindo classification. Time to recurrence (TTR): time from the start of the study to the first documented recurrence. Progression-free survival (PFS): time from the start of the study to tumor progression (in any aspect) or death from any cause. Overall survival (OS): time from the start of the study to death from any cause. Treatment schedule: The maximum interval between participant screening and initiation of treatment is 3 weeks (≤21 days). PD-1/CTLA-4 combination antibody: Eparaplimab Icotinib Injection, 5 mg/kg on Day 1, Day 22, and Day 43, administered intravenously, for a total of three cycles. Radiotherapy: Initiated within one week of starting immunotherapy, total dose DT: 30 Gy, 2.5 Gy × 12 fractions, once daily, five times per week. Surgery: Performed 3-5 weeks after completion of neoadjuvant therapy. Postoperative adjuvant therapy: Eparaplimab Icotinib Injection, 5 mg/kg on Day 1, every 3 weeks (Q3W), administered intravenously, continued up to 1 year. The study continues until disease progression, voluntary withdrawal by the patient, or occurrence of intolerable toxicities. Efficacy and safety assessments are conducted every two cycles (42 days ±7 days). If disease progression is observed (based on investigator evaluation or imaging evidence), the patient will voluntarily withdraw from the study; if intolerable toxicities occur, the participant should discontinue study treatment. In the event of treatment discontinuation for any reason, a final study visit should be conducted approximately 12 weeks after the last dose of study drug, to collect all possible adverse events and concomitant medication information. Follow-up of drug-related or possibly related adverse events should continue until the event stabilizes or resolves. A notice of study completion will be submitted to the hospital's Clinical Trial Management Center based on the date of the final follow-up visit of the last enrolled participant. An update and status annotation will also be made at the clinical trial registry.

Conditions

• Esophagogastric Junction/Gastric Adenocarcinoma

Interventions

Type	Name	Description
DRUG	PD-1/CTLA-4 combination antibody with low-dose radiotherapy	* PD-1/CTLA-4 combination antibody: Iparomlimab and Tuvonralimab， 5mg/kg on day 1, day 22, and day 43, administered via intravenous infusion, for a total of three cycles before surgery and maintained for up to 1 year after surgery. * Radiotherapy: To be conducted within one week of the start of immunotherapy, with a total dose of DT: 30Gy, 2.5Gy × 12 fractions, once daily, five times per week. The preoperative radiotherapy target area will be delineated by the radiation oncologist in accordance with the "NCCN Guidelines for Gastric/Esophagogastric Junction Cancers 2022" and in consultation with the opinions of the general surgeon. * Surgery: Surgical treatment will be completed within 3-5 weeks after the completion of neoadjuvant therapy. * Adjuvant therapy: Postoperative immunotherapy will be maintained for up to 1 year.

Timeline

• Start date: 2025-07-01
• Primary completion: 2027-12-01
• Completion: 2029-08-12
• First posted: 2025-07-08
• Last updated: 2025-07-08