Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
- Conditions
- Gastric Cancer
- Interventions
- Registration Number
- NCT05702229
- Lead Sponsor
- AstraZeneca
- Brief 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 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 240
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Substudy 6 AZD0901 AZD0901 plus AZD7789 and 5-fluorouracil or capecitabine Substudy 5 AZD7789 AZD7789 plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF) Substudy 3 AZD0901 AZD0901 plus volrustomig and 5-fluorouracil or capecitabine Substudy 2 Rilvegostomig Rilvegostomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF) Substudy 2 FOLFOX Rilvegostomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF) Substudy 1 XELOX Volrustomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF) Substudy 6 Capecitabine AZD0901 plus AZD7789 and 5-fluorouracil or capecitabine Substudy 1 Volrustomig Volrustomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF) Substudy 1 FOLFOX Volrustomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF) Substudy 3 5-Fluorouracil AZD0901 plus volrustomig and 5-fluorouracil or capecitabine Substudy 3 Capecitabine AZD0901 plus volrustomig and 5-fluorouracil or capecitabine Substudy 2 XELOX Rilvegostomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF) Substudy 4 AZD0901 AZD0901 plus rilvegostomig and 5-fluorouracil or capecitabine Substudy 5 FOLFOX AZD7789 plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF) Substudy 5 XELOX AZD7789 plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF) Substudy 3 Volrustomig AZD0901 plus volrustomig and 5-fluorouracil or capecitabine Substudy 4 Rilvegostomig AZD0901 plus rilvegostomig and 5-fluorouracil or capecitabine Substudy 6 AZD7789 AZD0901 plus AZD7789 and 5-fluorouracil or capecitabine Substudy 4 5-Fluorouracil AZD0901 plus rilvegostomig and 5-fluorouracil or capecitabine Substudy 4 Capecitabine AZD0901 plus rilvegostomig and 5-fluorouracil or capecitabine Substudy 6 5-Fluorouracil AZD0901 plus AZD7789 and 5-fluorouracil or capecitabine
- Primary Outcome Measures
Name Time Method ORR (per RECIST 1.1 as assessed by Investigator) Through substudy completion, an average of 2 years 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.
PFS6 (per RECIST 1.1 as assessed by Investigator) Through substudy completion, an average of 2 years the proportion of participants alive and progression-free at 6 months.
- Secondary Outcome Measures
Name Time Method other safety related endpoints Through substudy completion, an average of 2 years Incidence of AEs, AESIs, and SAEs.
PFS per RECIST 1.1 as assessed by the Investigator Through substudy completion, an average of 2 years 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.
OS Through substudy completion, an average of 2 years the time from the start of study intervention until the date of death due to any cause.
DoR per RECIST 1.1 based on Investigator assessment. Through substudy completion, an average of 2 years 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.
Trial Locations
- Locations (1)
Research Site
🇬🇧Oxford, United Kingdom