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: Active, not recruiting
• 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 City, China, 100080
    • 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
  • Guangzhou, China, 510655
    • The Sixth Affiliated Hospital of Sun Yat-sen University
  • Hangzhou City, China, 310003
    • The First Affiliated Hospital, Zhejiang University
  • Hangzhou City, China, 310016
    • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Hefei, China, 230601
    • The Second Affiliated Hospital of Anhui Medical University
  • Jining, China, 272000
    • Affiliated Hopsital of Jining Medical University
  • Nanjing City, China, 210008
    • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
  • Nantong City, China, 226361
    • Nan Tong Tumor Hospital
  • Taiyuan City, China, 030013
    • Shanxi Province Cancer Hospital
  • Xi'an City, China, 710061
    • The First Affiliated Hospital of Xian Jiao Tong University
  • Zhengzhou, China, 450052
    • The First Affiliated Hospital of Zhengzhou 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 is defined as the proportion of participants with a complete response or a partial response on two consecutive occasions >= 4 weeks apart during Stage 1, as determined by the investigator according to RECIST v1.1.	Up to approximately 3-5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS after randomization is defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.	Randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) (up to approximately 3-5 years)
Duration of Response (DOR)	DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.	First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) (up to approximately 3-5 years)
Overall Survival (OS)	OS after randomization, defined as the time from randomization to death from any cause, regardless of stage.	Randomization to death from any cause (up to approximately 3-5 years)
Overall Survival (OS)	OS at specific timepoints.	At specific timepoints (up to approximately 3-5 years)
Disease Control Rate	Disease control rate is defined as the proportion of participants with stable disease for >= 12 weeks or a complete or a partial response, as determined by the investigator according to RECIST v1.1.	Up to approximately 3-5 years
Percentage of Participants with Adverse Events in Stage 1	Percentage of participants with adverse events in Stage 1.	Baseline through approximately end of study (approximately 3-5 years)
Percentage of Participants with Adverse Events in Stage 2	Percentage of participants with adverse events in Stage 2.	Baseline through approximately end of study (approximately 3-5 years)

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 (Estimated): December 31, 2024
• Study Completion (Estimated): June 22, 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 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Capecitabine; Oxaliplatin; Atezolizumab
• Other Study ID Numbers: YO43408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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