A Study of Novel Agents or Combinations as Perioperative Treatment in Participants With Locally Advanced Resectable Gastroesophageal Adenocarcinoma

Not Applicable

Not yet recruiting

• Conditions: Gastroesophageal Adenocarcinoma
• Interventions: Drug: AZD0901; Drug: Rilvegostomig; Drug: Trastuzumab Deruxtecan (T-DXd); Drug: FLOT Chemotherapy; Drug: Capecitabine; Drug: 5-Fluorouracil (5-FU)

• Registration Number: NCT07069712
• Lead Sponsor: AstraZeneca

Brief Summary

GEMINI-PeriOp GC study will assess the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of novel agents or novel combinations as perioperative treatment in participants with locally advanced resectable gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma who have not received previous treatment for the disease.

Detailed Description

This Phase II, open-label, multi-drug, multi-center platform study consists of individual sub-studies, each allows the assessment of multiple novel agents or novel combinations.

Participants will be assigned across 3 sub-studies, to have sufficient evaluable participants of the confirmed recommended dose by Safety Review Committee (SRC) for study intervention in each corresponding sub-study.

Study Timeline

• Study First Submitted: 2025-06-24
• Status Verified: 2025-07
• Study First Submitted QC: 2025-07-07
• Last Update Submitted: 2025-07-07
• Study Start: 2025-07-14
• Study First Posted: 2025-07-17
• Last Update Posted: 2025-07-17
• Primary Completion: 2026-12-18
• Study Completion: 2028-09-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Histologically documented gastric, GEJ, or esophageal adenocarcinoma with resectable disease
• Participants who are CLDN18.2-positive and HER2-negative in Sub-study 1 or HER2-positive in Sub-study 2; no specific requirements for Sub-study 3
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ and bone marrow function
• Body weight > 35 kg

Exclusion Criteria

• Participants had any prior anti-cancer treatment or surgery for the current gastric, GEJ, or esophageal cancer.
• Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment
• Central nervous system (CNS) pathology
• Uncontrolled infections
• Participants with history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, current ILD/pneumonitis, or suspected ILD/pneumonitis
• History of another primary malignancy
• Participants with any known or suspicious distant metastasis
• Uncontrolled hepatitis B and/or chronic or active hepatitis B
• Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sub-study 1: AZD0901 plus rilvegostomig and 5-FU or capecitabine	AZD0901	Participants will receive AZD0901 plus rilvegostomig and 5-FU or capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).
Sub-study 1: AZD0901 plus rilvegostomig and 5-FU or capecitabine	Rilvegostomig	Participants will receive AZD0901 plus rilvegostomig and 5-FU or capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).
Sub-study 1: AZD0901 plus rilvegostomig and 5-FU or capecitabine	Capecitabine	Participants will receive AZD0901 plus rilvegostomig and 5-FU or capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).
Sub-study 1: AZD0901 plus rilvegostomig and 5-FU or capecitabine	5-Fluorouracil (5-FU)	Participants will receive AZD0901 plus rilvegostomig and 5-FU or capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).
Sub-study 2: T-DXd plus rilvegostomig and 5-FU or capecitabine	Rilvegostomig	Participants will receive T-DXd plus rilvegostomig and 5-FU or capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).
Sub-study 2: T-DXd plus rilvegostomig and 5-FU or capecitabine	Trastuzumab Deruxtecan (T-DXd)	Participants will receive T-DXd plus rilvegostomig and 5-FU or capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).
Sub-study 2: T-DXd plus rilvegostomig and 5-FU or capecitabine	Capecitabine	Participants will receive T-DXd plus rilvegostomig and 5-FU or capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).
Sub-study 2: T-DXd plus rilvegostomig and 5-FU or capecitabine	5-Fluorouracil (5-FU)	Participants will receive T-DXd plus rilvegostomig and 5-FU or capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).
Sub-study 3: Rilvegostomig plus FLOT chemotherapy	Rilvegostomig	Participants will receive Rilvegostomig plus FLOT chemotherapy as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).
Sub-study 3: Rilvegostomig plus FLOT chemotherapy	FLOT Chemotherapy	Participants will receive Rilvegostomig plus FLOT chemotherapy as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events (AEs) and serious adverse events (SAEs)	Until sub-study completion, up to 38 months	To assess the safety and tolerability of perioperative treatment.
Percentage of participants with pathological complete response (pCR)	Until sub-study completion, up to 38 months	pCR is defined as no viable cancer cells, including lymph nodes after complete evaluation in the resected gastric, GEJ, or esophageal cancer specimen and all sampled regional lymph nodes following neoadjuvant treatment.

Secondary Outcome Measures

Name	Time	Method
Percentage of participants with tumor downstaging	Until sub-study completion, up to 38 months	Tumor downstaging is defined as the lowering of the primary tumor (T) and/or regional lymph nodes (N) from pre-neoadjuvant clinical staging (pre-cTN) to post-neoadjuvant clinical staging (post-cTN) and to postoperative pathological staging (ypTN).
Disease-free survival (DFS)	Until sub-study completion, up to 38 months	DFS is defined as the time elapsed from the date of the first post-surgery scan (ie, Adjuvant Baseline scan) until the date of first evidence of disease recurrence as determined by Investigator using RECIST 1.1 assessment (local or distant), or death due to any cause, whichever occurs first.
Serum concentrations of study interventions	Until sub-study completion, up to 38 months	To assess the serum concentrations of study interventions in participants receiving perioperative treatment.
Surgery completion rate as planned	Until sub-study completion, up to 38 months	Surgery completion rate (including R0 and R1) as planned is defined as the percentage of participants who received intended gastrectomy or gastroesophagectomy as planned.
R0 resection (complete resection) rate as planned	Until sub-study completion, up to 38 months	R0 resection (complete resection) rate as planned is the percentage of participants who received gastrectomy or gastroesophagectomy and had a confirmed margin-negative resection as planned.
Overall survival (OS)	Until sub-study completion, up to 38 months	OS is defined as the time from the first dose of the study intervention until the date of death due to any cause regardless of whether participant withdraws from treatment or receives another anti-cancer therapy.
Event-free survival (EFS)	Until sub-study completion, up to 38 months	EFS is defined as the time from the first dose of study intervention to documented Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or non-RECIST 1.1 disease progression that precludes radical surgery or requires non-protocol therapy during the neoadjuvant through surgery period, or to documented RECIST 1.1 or biopsy-confirmed non-RECIST 1.1 recurrence or progression of disease during the adjuvant period, or death due to any cause at any time.
Objective response rate (ORR)	Until sub-study completion, up to 38 months	ORR is defined as the percentage of participants who have a CR or PR as determined by Investigator using RECIST 1.1 at their latest assessment prior to surgery.
Number of participants with positive anti-drug antibodies (ADA)	Until sub-study completion, up to 38 months	To assess the immunogenicity of study interventions in participants receiving perioperative treatment.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Headington, United Kingdom