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

AstraZeneca

Status and phase: Enrolling; Phase 2

Conditions: Gastric Cancer

Treatments: Drug: 5-Fluorouracil; Drug: XELOX; Drug: Rilvegostomig; Drug: AZD0901; Drug: Capecitabine; Drug: FOLFOX; Drug: Volrustomig

Study type: Interventional

Funder types: Industry

Identifiers

NCT05702229

2022-002840-29 (EudraCT Number)

2024-510977-27-00 (EU Trial (CTIS) Number)

D7986C00001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 163 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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163 participants in 6 patient groups

Substudy 1

Experimental group

Description:

Volrustomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)

Treatment:

Drug: Volrustomig

Drug: FOLFOX

Drug: XELOX

Substudy 2

Experimental group

Description:

Rilvegostomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)

Treatment:

Drug: FOLFOX

Drug: Rilvegostomig

Drug: XELOX

Substudy 3

Experimental group

Description:

AZD0901 plus volrustomig and 5-fluorouracil or capecitabine

Treatment:

Drug: Volrustomig

Drug: Capecitabine

Drug: AZD0901

Drug: 5-Fluorouracil

Substudy 4, Cohort 4a1

Experimental group

Description:

Sonesitatug vedotin (AZD0901) plus rilvegostomig and 5-fluorouracil or capecitabine

Treatment:

Drug: Capecitabine

Drug: AZD0901

Drug: Rilvegostomig

Drug: 5-Fluorouracil

Substudy 4, Cohort 4a2

Experimental group

Description:

Sonesitatug vedotin (AZD0901) plus rilvegostomig and 5-fluorouracil

Treatment:

Drug: AZD0901

Drug: Rilvegostomig

Drug: 5-Fluorouracil

Substudy 4, Cohort 4b

Experimental group

Description:

Sonesitatug vedotin (AZD0901) plus capecitabine

Treatment:

Drug: Capecitabine

Drug: AZD0901