Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

An Open-Label, Multi-Drug, Multi-Centre, Phase II Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

This is a Phase II, open-label, multi-drug, multi-centre study designed to assess the efficacy, safety, tolerability, pharmacokinetics, and immunogenicity of novel combination therapies in participants with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: FOLFOX; Drug: XELOX; Drug: Volrustomig; Drug: Rilvegostomig; Drug: AZD0901; Drug: 5-Fluorouracil; Drug: Capecitabine; Drug: AZD7789

Detailed Description

Approximately 240 participants will be assigned across 6 substudies, with approximately 40 evaluable participants of the confirmed recommend dose by SRC for study intervention in each corresponding substudy.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• China
  • Beijing, China, 100142
    • Recruiting
    • Research Site
  • Hangzhou, China, 310020
    • Recruiting
    • Research Site
  • Hangzhou, China, 310003
    • Recruiting
    • Research Site
  • Harbin, China, 150081
    • Recruiting
    • Research Site
  • Hefei, China, 230031
    • Recruiting
    • Research Site
  • Kunming, China, 650118
    • Not yet recruiting
    • Research Site
  • Wuhan, China, 430079
    • Recruiting
    • Research Site
  • Yinchuan, China, 750004
    • Recruiting
    • Research Site
  • Zhengzhou, China
    • Recruiting
    • Research Site
• Japan
  • Kashiwa, Japan, 227-8577
    • Recruiting
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Not yet recruiting
    • Research Site
  • Tokyo, Japan, 104-0045
    • Recruiting
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Research Site
  • Elche(Alicante), Spain, 03202
    • Recruiting
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 08908
    • Recruiting
    • Research Site
  • Madrid, Spain, 28007
    • Recruiting
    • Research Site
  • Madrid, Spain, 28040
    • Recruiting
    • Research Site
  • Santander, Spain, 39008
    • Recruiting
    • Research Site
• Taiwan
  • Hsinchu, Taiwan, 300
    • Recruiting
    • Research Site
  • Kaohsiung, Taiwan, 80756
    • Recruiting
    • Research Site
  • Taichung, Taiwan, 404
    • Recruiting
    • Research Site
  • Tainan City, Taiwan, 70403
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 10002
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 11259
    • Recruiting
    • Research Site
  • Taoyuan City, Taiwan, 333
    • Recruiting
    • Research Site
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Suspended
    • Research Site
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • Research Site
  • London, United Kingdom, EC1M 6BQ
    • Not yet recruiting
    • Research Site
  • Oxford, United Kingdom, OX3 7LE
    • Recruiting
    • Research Site
• United States
  • California
    • Los Angeles, California, United States, 90017
      • Recruiting
      • Research Site
    • Los Angeles, California, United States, 90095
      • Withdrawn
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70817
      • Recruiting
      • Research Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Research Site
  • New York
    • Bronx, New York, United States, 10469
      • Recruiting
      • Research Site
    • New Hyde Park, New York, United States, 11042
      • Recruiting
      • Research Site
    • New York, New York, United States, 10028
      • Recruiting
      • Research Site
    • New York, New York, United States, 11210
      • Recruiting
      • Research Site
    • Shirley, New York, United States, 11967
      • Recruiting
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years or older at the time of signing the ICF.
• Body weight > 35 kg.
• Previously untreated for unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
• Has measurable target disease assessed by the Investigator based on RECIST 1.1.
• ECOG PS zero or one.
• Life expectancy of at least 12 weeks.
• Adequate organ and bone marrow function.
• Has central lab confirmed Claudin18.2 status at screening from archival tumour collected within past 24 months or from a fresh biopsy when Substudy 3, Substudy 4 or Substudy 6 is open for recruitment.

Exclusion Criteria:

• Participants with HER2-positive (3+ by IHC, or 2+ by IHC and positive by in situhybridisation) or indeterminate gastric or GEJ carcinoma.
• Untreated or progressive CNS metastatic disease, any leptomeningeal disease, or cord compression.
• Participants with ascites which cannot be controlled with appropriate interventions.
• Active infectious diseases, including tuberculosis, HIV infection, or hepatitis B/C.
• Uncontrolled intercurrent illness.
• Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment.
• History of another primary malignancy.
• Previous treatment with an immune-oncology agent.
• Previous treatment with any modalities of Claudin18.2 target therapy or MMAE exposure (when Substudy 3, Substudy 4, or Substudy 6 is open for recruitment).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Substudy 1; Volrustomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)	Drug: FOLFOX; 5-fluorouracil 400 mg/m^2 IV, oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2 (or levoleucovorin 200 mg/m^2 when locally preferred and available), day 1, 5-fluorouracil 1200 mg/m^2 IV 24 h day 1-2; Drug: XELOX; capecitabine 1000 mg/m^2 BID, days 1 to 14, oxaliplatin 130 mg/m^2, day 1; Drug: Volrustomig; an anti PD-1 and anti CTLA-4 bispecific antibody; IV infusion
Experimental: Substudy 2; Rilvegostomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)	Drug: FOLFOX; 5-fluorouracil 400 mg/m^2 IV, oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2 (or levoleucovorin 200 mg/m^2 when locally preferred and available), day 1, 5-fluorouracil 1200 mg/m^2 IV 24 h day 1-2; Drug: XELOX; capecitabine 1000 mg/m^2 BID, days 1 to 14, oxaliplatin 130 mg/m^2, day 1; Drug: Rilvegostomig; an anti PD-1 and anti-TIGIT bispecific antibody; IV infusion
Experimental: Substudy 3; AZD0901 plus volrustomig and 5-fluorouracil or capecitabine	Drug: Volrustomig; an anti PD-1 and anti CTLA-4 bispecific antibody; IV infusion; Drug: AZD0901; an anti Claudin18.2 ADC; IV infusion; Drug: 5-Fluorouracil; 5-FU, IV infusion, Q3W; Drug: Capecitabine; Oral take, Q3W
Experimental: Substudy 4; AZD0901 plus rilvegostomig and 5-fluorouracil or capecitabine	Drug: Rilvegostomig; an anti PD-1 and anti-TIGIT bispecific antibody; IV infusion; Drug: AZD0901; an anti Claudin18.2 ADC; IV infusion; Drug: 5-Fluorouracil; 5-FU, IV infusion, Q3W; Drug: Capecitabine; Oral take, Q3W
Experimental: Substudy 5; AZD7789 plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)	Drug: FOLFOX; 5-fluorouracil 400 mg/m^2 IV, oxaliplatin 85 mg/m^2, leucovorin 400 mg/m^2 (or levoleucovorin 200 mg/m^2 when locally preferred and available), day 1, 5-fluorouracil 1200 mg/m^2 IV 24 h day 1-2; Drug: XELOX; capecitabine 1000 mg/m^2 BID, days 1 to 14, oxaliplatin 130 mg/m^2, day 1; Drug: AZD7789; an anti PD 1 and anti TIM 3 bispecific antibody; IV infusion
Experimental: Substudy 6; AZD0901 plus AZD7789 and 5-fluorouracil or capecitabine	Drug: AZD0901; an anti Claudin18.2 ADC; IV infusion; Drug: 5-Fluorouracil; 5-FU, IV infusion, Q3W; Drug: Capecitabine; Oral take, Q3W; Drug: AZD7789; an anti PD 1 and anti TIM 3 bispecific antibody; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR (per RECIST 1.1 as assessed by Investigator)	the proportion of participants who have a confirmed complete response or confirmed partial response, as determined by the Investigator at local site per RECIST 1.1.	Through substudy completion, an average of 2 years
PFS6 (per RECIST 1.1 as assessed by Investigator)	the proportion of participants alive and progression-free at 6 months.	Through substudy completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS per RECIST 1.1 as assessed by the Investigator	the time from the start of study intervention until progression per RECIST 1.1 as assessed by the Investigator at the local site or death due to any cause in the absence of progression.	Through substudy completion, an average of 2 years
OS	the time from the start of study intervention until the date of death due to any cause.	Through substudy completion, an average of 2 years
DoR per RECIST 1.1 based on Investigator assessment.	the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 by the Investigator at local site or death due to any cause in the absence of disease progression.	Through substudy completion, an average of 2 years
other safety related endpoints	Incidence of AEs, AESIs, and SAEs.	Through substudy completion, an average of 2 years

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2023
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: January 18, 2023
• First Posted (Actual): January 27, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Gastric adenocarcinoma; Locally advanced; GEJ adenocarcinoma; Metatstatic; GEMINI-Gastric
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fluorouracil; Capecitabine
• Other Study ID Numbers: D7986C00001; 2022-002840-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No