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RecruitingInterventionalPhase 2

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

NCT ID: NCT05702229Sponsor: AstraZenecaLast updated: 2026-05-14

Summary

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.

Detailed description

Approximately 360 participants will be assigned across 4 substudies, with approximately 60 evaluable participants of the confirmed recommend dose by SRC for study intervention in each corresponding substudy/cohort.

Arms & interventions

  • DrugRilvegostomig

    an anti PD-1 and anti-TIGIT bispecific antibody; IV infusion

  • DrugVolrustomig

    an anti PD-1 and anti CTLA-4 bispecific antibody; IV infusion

  • DrugFOLFOX

    5-fluorouracil oxaliplatin, leucovorin (levoleucovorin when locally preferred and available)

  • DrugXELOX

    capecitabine and oxaliplatin

  • DrugAZD0901

    an anti Claudin18.2 ADC; IV infusion

  • Drug5-Fluorouracil

    5-FU, IV infusion

  • DrugCapecitabine

    Oral take

Outcome measures

Primary

  • 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.

    Time frame: 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.

    Time frame: Through substudy completion, an average of 2 years

Secondary

  • PFS per RECIST 1.1 as assessed by the Investigator

    Time frame: Through substudy completion, an average of 2 years

  • OS

    Time frame: Through substudy completion, an average of 2 years

  • other safety related endpoints

    Time frame: Through substudy completion, an average of 2 years

  • DoR per RECIST 1.1 based on Investigator assessment.

    Time frame: Through substudy completion, an average of 2 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 i s 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 is open for recruitment).

Study locations (11)

Research Site

Los Angeles, California, 90017

Recruiting

Research Site

Los Angeles, California, 90095

Withdrawn

Research Site

Baton Rouge, Louisiana, 70817

Recruiting

Research Site

Grand Rapids, Michigan, 49503

Recruiting

Research Site

New Hyde Park, New York, 11042

Withdrawn

Research Site

New York, New York, 10028

Withdrawn

Research Site

New York, New York, 10065

Recruiting

Research Site

New York, New York, 11210

Withdrawn

Research Site

Shirley, New York, 11967

Withdrawn

Research Site

The Bronx, New York, 10469

Withdrawn

Research Site

Pittsburgh, Pennsylvania, 15212

Withdrawn