An Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Gastric or Gastroesophageal Junction Carcinoma

NCT05251948 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: YO43408
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 11

Brief Summary

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced gastric carcinoma (GC) or gastroesophageal junction carcinoma (GEJC). The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and modify the participant population. Cohort 1 will enroll participants with inoperable locally advanced, metastatic, or advanced GC or GEJC, with adenocarcinoma confirmed as the predominant histology, who have not received prior systemic therapy for advanced or metastatic disease. Eligible participants will initially be randomly assigned to one of treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.

Conditions

Gastric and Gastroesophageal Junction Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions, ≥ 4 weeks apart during Stage 1, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to \< 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. Percentages have been rounded off.

  Up to 42.1 months

Secondary Outcomes (6)

• Progression-free Survival (PFS) After Randomization

  From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to 42.1 months)

• Overall Survival (OS) After Randomization

  From randomization to death from any cause (up to 42.1 months)

• OS Rates at Specified Timepoints

  At Months 6 and 12

• Duration of Response (DOR)

  From first occurrence of CR or PR to PD or death from any cause, whichever occurred first (up to 42.1 months)

• Disease Control Rate (DCR)

  Up to 42.1 months

Other Outcomes (1)

• Number of Participants With AEs in Stage 2

  Up to 42.1 months

Study Arms (2)

Atezo + CAPOX (capecitabine + oxaliplatin)

ACTIVE COMPARATOR

Participants in the atezolizumab plus capecitabine plus oxaliplatin in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Drug: Atezolizumab; Drug: Capecitabine; Drug: Oxaliplatin

Atezo + CAPOX +Tira

EXPERIMENTAL

Participants in the atezolizumab plus capecitabine plus oxaliplatin plus tiragolumab arm in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Drug: Atezolizumab; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Tiragolumab

Interventions

Atezolizumab DRUG

Atezolizumab is administered by IV infusion on Day 1 of each 21 day cycle. Treatment until progressive disease.

Also known as: Tecentriq

Atezo + CAPOX (capecitabine + oxaliplatin); Atezo + CAPOX +Tira

Capecitabine DRUG

Capecitabine is administered orally twice daily on Days 1-14 of each 21 day cycle. Treatment for up to six cycles.

Atezo + CAPOX (capecitabine + oxaliplatin); Atezo + CAPOX +Tira

Oxaliplatin DRUG

Oxaliplatin is administered by IV infusion on Day 1 of each 21 day cycle. Treatment for up to six cycles.

Atezo + CAPOX (capecitabine + oxaliplatin); Atezo + CAPOX +Tira

Tiragolumab DRUG

Tiragolumab is administered by IV infusion on Day 1 of each 21 day cycle.

Atezo + CAPOX +Tira

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG Performance Status of 0 or 1
• Inoperable locally advanced, metastatic, or advanced GC or GEJC, with adenocarcinoma confirmed as the predominant histology
• No prior systemic treatment for advanced or metastatic disease
• Life expectancy \>= 3 months, as determined by the investigator
• Human epidermal growth factor receptor 2 (HER2)-negative tumors
• Measurable disease according to RECIST v1.1
• Adequate hematologic and end-organ function
• Patients without hepatitis B virus (HBV) infection at screening
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
• Negative HIV test at screening
• For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, as outlined for each specific treatment arm
• For men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

You may not qualify if:

• Prior treatment with CD137 agonists or immune checkpoint blockade therapies
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Any contraindications to any of the study drugs of the chemotherapy regimen
• Eligible only for the control arm
• Patients with a signet ring cells dominant carcinoma
• Symptomatic, untreated, or actively progressing CNS metastases
• History of leptomeningeal disease
• Active or history of autoimmune disease or immune deficiency
• Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• History of malignancy other than GC or GEJC within 2 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death
• Prior treatment with an anti-TIGIT agent
• Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (11)

The General Hospital of People?s Liberation Army (301 Hospital)

Beijing, 100853, China

Location

the First Hospital of Jilin University

Changchun, 130021, China

Location

First Affiliated Hospital of Gannan Medical University

Ganzhou, 341000, China

Location

The First Affiliated Hospital, Zhejiang University

Hangzhou, 310003, China

Location

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

Hangzhou, 310016, China

Location

The Second Affiliated Hospital of Anhui Medical University

Hefei, 230601, China

Location

Affiliated Hopsital of Jining Medical University

Jining, 272000, China

Location

Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School

Nanjing, 210008, China

Location

Nan Tong Tumor Hospital

Nantong, 226361, China

Location

Shanxi Province Cancer Hospital

Taiyuan, 030013, China

Location

The First Affiliated Hospital of Xian Jiao Tong University

Xi'an, 710061, China

Location

MeSH Terms

Interventions

atezolizumab; Capecitabine; Oxaliplatin; Tiragolumab

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: February 23, 2022
• Study Start: March 1, 2022
• Primary Completion: September 4, 2025
• Study Completion: September 4, 2025
• Last Updated: April 15, 2026
• Results First Posted: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (11)