NCT07290985

AACR Adaptive Biomarker-Driven Organ Preservation Trial in Gastroesophageal Adenocarcinomas

AACR Adaptive Biomarker-Driven Organ Preservation Trial In Gastroesophageal Adenocarcinomas (AACR-ADOPT-GEA)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 121 (estimated)
• Sponsor: American Association for Cancer Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will test a new personalized treatment approach for patients with stomach or esophageal cancer. It will take place in two stages and aims to find the best combination of chemotherapy, immunotherapy, and targeted drugs based on each patient's tumor biomarkers. Upon enrollment onto the study, patients will consent to tumor biomarker testing and may receive one cycle of standard chemotherapy while awaiting results. Those with a matching biomarker will join the corresponding treatment group that combines chemotherapy, an immune checkpoint inhibitor, and/or a targeted therapy. In Stage I of the study, treatment lasts about four months before surgery, followed by an additional eight months of therapy for a total of one year. The most effective treatments from Stage I will be studied further in Stage II of the study to see whether some patients can safely avoid surgery. Those patients enrolled during Stage II will receive four months of the same combination treatment (chemotherapy, an immune checkpoint inhibitor, and/or a targeted therapy) but may be eligible to skip surgery if their cancer completely disappears after pre-surgery therapy. All patients will then receive an additional eight months of therapy and those who skipped surgery will be closely monitored with scans and endoscopies.

Detailed description

This is a two-stage, prospective, multi-center, perioperative, biomarker-driven, open-label study. The trial design consists of a screening phase (Stage I) and a testing phase (Stage II). Stage I: Eligible patients will provide screening consent and research tissue for biomarker assessment. While awaiting results, they may receive one cycle of FLOT or mFOLFOX6. Once a biomarker included in the study platform is identified, patients will sign a second consent and be assigned to the corresponding subgroup. They will continue treatment with the chemotherapy backbone (mFOLFOX6) plus an immune checkpoint inhibitor and a biomarker-targeted agent. Patients who began on FLOT will switch to mFOLFOX6 once a targeted agent is added. If no actionable biomarker is detected, patients will continue standard-of-care therapy off-study. Patients receiving the chemotherapy + immune checkpoint inhibitor + targeted agent combination will complete 4 months of preoperative therapy, followed by surgery and postoperative therapy for a total treatment duration of up to one year. Once 24 patients in a given biomarker subgroup have undergone surgery, continuation to Stage II will depend on meeting predefined efficacy thresholds. Only regimens demonstrating sufficient efficacy will advance. Stage II: Effective therapies identified in Stage I will be further evaluated to establish predictive markers of pathological complete response (pathCR) and identify patients who may safely avoid surgery. Patients will provide tissue for central biomarker testing and may receive a chemotherapy cycle while awaiting results. Once assigned to an eligible biomarker subgroup, they will receive mFOLFOX6 + immune checkpoint inhibitor plus the targeted agent for 4 months. Response will be assessed through clinical, endoscopic, and radiologic evaluation. Patients showing no residual disease after preoperative therapy will forgo surgery and continue maintenance therapy (immune checkpoint inhibitor plus the targeted agent) for an additional 8 months with regular surveillance. Those with residual disease will proceed to surgery, followed by postoperative therapy and follow-up for up to one year.

Conditions

• Gastroesophageal Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Tislelizumab	150 mg every 2 weeks for 4 months pre-operatively and up to 8 months post-operatively
DRUG	Leucovorin	400 mg/m² every 2 weeks for 4 months pre-operatively and up to 8 months post-operatively
DRUG	Oxaliplatin	85 mg/m² every 2 weeks for 4 months pre-operatively and up to 8 months post-operatively
DRUG	Fluorouracil	2,400 mg/m² every 2 weeks for 4 months pre-operatively and up to 8 months post-operatively
DRUG	Zanidatamab	1,200 mg for patients weighing less than 70 kg and 1,600 mg for patients weighing 70 kg or more every 2 weeks for 4 months pre-operatively and up to 8 months post-operatively

Timeline

• Start date: 2026-05-01
• Primary completion: 2028-06-01
• Completion: 2028-12-01
• First posted: 2025-12-18
• Last updated: 2026-04-07

Regulatory

• FDA-regulated drug study