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

Purpose

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.

Condition

  • Gastroesophageal Adenocarcinoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Sub-study 1: AZD0901 plus Rilvegostomig and 5-FU or 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.
  • Drug: AZD0901
    AZD0901 will be administered as an IV infusion.
    Other names:
    • Sonesitatug Vedotin
  • Drug: Rilvegostomig
    Rilvegostomig will be administered as an IV infusion.
    Other names:
    • AZD2936
  • Drug: Capecitabine
    Capecitabine (Fluoropyrimidine) will be administered orally as chemotherapy standard of care.
  • Drug: 5-Fluorouracil (5-FU)
    5-FU (Fluoropyrimidine) will be administered as an IV infusion as chemotherapy standard of care.
Experimental
Sub-study 2: T-DXd plus Rilvegostomig and 5-FU or 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.
  • Drug: Rilvegostomig
    Rilvegostomig will be administered as an IV infusion.
    Other names:
    • AZD2936
  • Drug: Trastuzumab Deruxtecan (T-DXd)
    T-DXd will be administered as an IV infusion.
    Other names:
    • DS-8201a
  • Drug: Capecitabine
    Capecitabine (Fluoropyrimidine) will be administered orally as chemotherapy standard of care.
  • Drug: 5-Fluorouracil (5-FU)
    5-FU (Fluoropyrimidine) will be administered as an IV infusion as chemotherapy standard of care.
Experimental
Sub-study 3: Rilvegostomig plus 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.
  • Drug: Rilvegostomig
    Rilvegostomig will be administered as an IV infusion.
    Other names:
    • AZD2936
  • Drug: FLOT Chemotherapy
    FLOT (5-FU, leucovorin, oxaliplatin, and docetaxel) Chemotherapy will be administered as an IV infusion.

Recruiting Locations

Research Site
Newark, Delaware 19713

Research Site
Washington D.C., District of Columbia 20007

Research Site
Fairway, Kansas 66205

Research Site
North Shores, Michigan 49444

Research Site
New York, New York 10065

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

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.