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

AstraZeneca

Status and phase: Not yet enrolling; Phase 2

Conditions: Gastroesophageal Adenocarcinoma

Treatments: Drug: Rilvegostomig; Drug: 5-Fluorouracil (5-FU); Drug: Capecitabine; Drug: AZD0901; Drug: Trastuzumab Deruxtecan (T-DXd); Drug: FLOT Chemotherapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT07069712

2024-516909-23-00 (Other Identifier)

D9804C00001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 3 patient groups

Sub-study 1: AZD0901 plus rilvegostomig and 5-FU or capecitabine

Experimental group

Description:

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).

Treatment:

Drug: Rilvegostomig

Drug: 5-Fluorouracil (5-FU)

Drug: AZD0901

Drug: Capecitabine

Sub-study 2: T-DXd plus rilvegostomig and 5-FU or capecitabine

Experimental group

Description:

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).

Treatment:

Drug: Rilvegostomig

Drug: 5-Fluorouracil (5-FU)

Drug: Trastuzumab Deruxtecan (T-DXd)

Drug: Capecitabine

Sub-study 3: Rilvegostomig plus FLOT chemotherapy

Experimental group

Description:

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).

Treatment:

Drug: Rilvegostomig

Drug: FLOT Chemotherapy