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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05702229
• Other study ID #: D7986C00001
• Secondary ID: 2022-002840-29
• Status: Recruiting
• Phase: Phase 2
• Start date: January 16, 2023
• Est. completion date: March 31, 2026

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: March 31, 2026
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer

Intervention

Drug:
• Rilvegostomig
an anti PD-1 and anti-TIGIT bispecific antibody; IV infusion
• Volrustomig
an anti PD-1 and anti CTLA-4 bispecific antibody; IV infusion
• 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
• XELOX
capecitabine 1000 mg/m^2 BID, days 1 to 14, oxaliplatin 130 mg/m^2, day 1
• AZD7789
an anti PD 1 and anti TIM 3 bispecific antibody; IV infusion
• AZD0901
an anti Claudin18.2 ADC; IV infusion
• 5-Fluorouracil
5-FU, IV infusion, Q3W
• Capecitabine
Oral take, Q3W

Locations

Country	Name	City	State
China	Research Site	Beijing
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Kunming
China	Research Site	Wuhan
China	Research Site	Yinchuan
China	Research Site	Zhengzhou
Japan	Research Site	Kashiwa
Japan	Research Site	Sunto-gun
Japan	Research Site	Tokyo
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Spain	Research Site	Barcelona
Spain	Research Site	Elche(Alicante)
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Santander
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan City
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	Oxford
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Bronx	New York
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	New Hyde Park	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Shirley	New York

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  China,  Japan,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Through substudy completion, an average of 2 years
Primary	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	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
Secondary	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
Secondary	other safety related endpoints	Incidence of AEs, AESIs, and SAEs.	Through substudy completion, an average of 2 years
Secondary	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