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

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Gastric or Gastroesophageal Junction Carcinoma (MORPHEUS C-Gastric and Gastroesophageal Junction Carcinoma)

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.

Study Overview

• Status: Terminated
• Conditions: Gastric and Gastroesophageal Junction Carcinoma
• Intervention / Treatment: Drug: Atezolizumab; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Tiragolumab

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100853
    • The General Hospital of People?s Liberation Army (301 Hospital)
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Ganzhou, China, 341000
    • First Affiliated Hospital of Gannan Medical University
  • Hangzhou, China, 310016
    • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
  • Hangzhou, China, 310003
    • The First Affiliated Hospital, Zhejiang University
  • Hefei, China, 230601
    • The Second Affiliated Hospital of Anhui Medical University
  • Jining, China, 272000
    • Affiliated Hopsital of Jining Medical University
  • Nanjing, China, 210008
    • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
  • Nantong, China, 226361
    • Nan Tong Tumor Hospital
  • Taiyuan, China, 030013
    • Shanxi Province Cancer Hospital
  • Xi'an, China, 710061
    • The First Affiliated Hospital of Xian Jiao Tong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for Stage 1:

• 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

Exclusion Criteria for Stage 1:

• 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

Exclusion Criteria for Tiragolumab-Containing Arm:

• Prior treatment with an anti-TIGIT agent
• Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atezo + CAPOX (capecitabine + oxaliplatin); 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; Atezolizumab is administered by IV infusion on Day 1 of each 21 day cycle. Treatment until progressive disease.; Other Names: Tecentriq; Drug: Capecitabine; Capecitabine is administered orally twice daily on Days 1-14 of each 21 day cycle. Treatment for up to six cycles.; Drug: Oxaliplatin; Oxaliplatin is administered by IV infusion on Day 1 of each 21 day cycle. Treatment for up to six cycles.
Experimental: Atezo + CAPOX +Tira; 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; Atezolizumab is administered by IV infusion on Day 1 of each 21 day cycle. Treatment until progressive disease.; Other Names: Tecentriq; Drug: Capecitabine; Capecitabine is administered orally twice daily on Days 1-14 of each 21 day cycle. Treatment for up to six cycles.; Drug: Oxaliplatin; Oxaliplatin is administered by IV infusion on Day 1 of each 21 day cycle. Treatment for up to six cycles.; Drug: Tiragolumab; Tiragolumab is administered by IV infusion on Day 1 of each 21 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) After Randomization	PFS after randomization was defined as the time from randomization to the first occurrence of PD or death from any cause (whichever occurred first) in Stage 1, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm. PFS was censored at the day of the last tumor assessment for participants who did not die or did not have documented PD. Median PFS was estimated using the Kaplan-Meier (K-M) method.	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	OS was defined as the time from randomization to death from any cause, regardless of stage. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. Median OS was estimated using the K-M method.	From randomization to death from any cause (up to 42.1 months)
OS Rates at Specified Timepoints	OS was defined as the time from randomization to death from any cause, regardless of stage. OS rate at 6 and 12 months was defined as the percentage of participants who did not experience death from any cause at these timepoints from randomization. OS rates at the specified timepoints were estimated using the K-M method. Percentages have been rounded off.	At Months 6 and 12
Duration of Response (DOR)	DOR was defined as time from the first occurrence of a documented objective response (OR), CR or PR to PD or death from any cause (whichever occurred first) in Stage 1, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target or non-target lesions. Any pathological lymph nodes (whether target/non-target lesions) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm. DOR was censored at the day of the last tumor assessment for participants who did not die or did not have documented PD. Median DOR was estimated using the K-M method.	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)	DCR was defined as percentage of participants with stable disease (SD) for ≥ 12 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. 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 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm. Percentages have been rounded off.	Up to 42.1 months
Number of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Up to 42.1 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With AEs in Stage 2	An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Up to 42.1 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Actual): September 4, 2025
• Study Completion (Actual): September 4, 2025

Study Registration Dates

• First Submitted: February 9, 2022
• First Submitted That Met QC Criteria: February 14, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; atezolizumab; Tiragolumab
• Other Study ID Numbers: YO43408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes