A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer)

December 9, 2025 updated by: Hoffmann-La Roche

A Phase Ib/II, Open-Label, Multicenter, Randomized, Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer)

A Phase Ib/II, open label, multi-center, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with locally advanced unresectable or metastatic G/GEJ cancer (hereafter referred to as gastric cancer) and esophageal cancer. Two cohorts of patients with gastric cancer have been enrolled in parallel in this study: the second-line (2L) Gastric Cancer Cohort consists of patients with gastric cancer who have progressed after receiving a platinum-containing or fluoropyrimide-containing chemotherapy regimen in the first-line setting, and the first-line (1L) Gastric Cancer Cohort consists of patients with gastric cancer who have not received prior chemotherapy in this setting. In each cohort, eligible patients will be assigned to one of several treatment arms. Additionally, a cohort of patients with esophageal cancer who have not received prior systemic treatment for their disease will be enrolled in this study. Eligible patients will be randomized to chemotherapy or the combination of chemotherapy with checkpoint inhibitor immunotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
214

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • New South Wales
      • Blacktown, New South Wales, Australia, 2148
        • Blacktown Hospital
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Medical Centre-Moorabbin Campus
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus
      • Tel Aviv, Israel, 64239
        • Sourasky Medical Centre
  • South Korea
      • Gyeonggi-do, South Korea, 13620
        • Seoul National University Bundang Hospital
      • Seoul, South Korea, 02841
        • Korea University Anam Hospital
      • Seoul, South Korea, 135-710
        • Samsung Medical Center
      • Seoul, South Korea, 03080
        • Seoul National University Hospital (SNUH) - Medical Oncology Center
      • Seoul, South Korea
        • Yonsei University College of Medicine (YUCM)-Yonsei Cancer Center
      • Songpa-gu, South Korea, 05505
        • University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC)
      • Suwon, South Korea, 442-723
        • The Catholic University of Korea St. Vincent's Hospital
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall dHebron
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Universidad de Navarra - Clinica Universitaria de Navarra (CUN)
  • Taiwan
      • Tainan, Taiwan, 70457
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
      • Zhongzheng Dist., Taiwan, 10051
        • National Taiwan University Hospital (NTUH) - Cancer Research Center
  • United Kingdom
      • Glasgow, United Kingdom, G12 0YN
        • Beatson West of Scotland Cancer Centre
      • London, United Kingdom, SW7 3RP
        • The Royal Marsden
      • London, United Kingdom
        • Barts and The London School of Medicine and Dentistry - Barts Cancer Institute (BCI)-CECM
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust
      • Sutton, United Kingdom, SM2 5PT
        • The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH) - Sutton
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Cancer Center
    • California
      • Los Angeles, California, United States, 90033
        • Uni of Southern California
      • Santa Monica, California, United States, 90404
        • UCLA Jonsson Comprehensive Cancer Center
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology - Nashville
    • Texas
      • Houston, Texas, United States, 77030-4000
        • The University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Gastric Cancer Cohorts Inclusion Criteria:

  • Age >/= 18 years;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
  • Life expectancy >/= 3 months, as determined by the investigator;
  • Histologically or cytologically confirmed locally advanced unresectable or metastatic adenocarcinoma of gastric or gastroesophageal junction; (for the 1L Gastric Cancer Cohort: no prior systemic therapy for the locally advanced or metastatic disease; for the 2L Gastric Cancer Cohort: disease progression during or following a first-line platinum-containing or fluoropyrimidine-containing chemotherapy regimen);
  • Availability of a representative tumor specimen that is suitable for determination of PD-L1 and TIGIT levels by IHC and/or additional biomarker status by means of retrospective central testing;
  • Only for the 1L Gastric Cancer Cohort: human epidermal growth factor receptor 2 (HER2)-negative tumors;
  • Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1);
  • Adequate hematologic and end organ function based on laboratory results obtained within 14 days prior to initiation of study treatment;
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm;
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm.

Esophageal Cancer Cohort Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of squamous cell carcinoma or adenocarcinoma of the esophagus in locally advanced or metastatic disease;
  • No prior systemic treatment for esophageal cancer, with the following exception:

For patients treated with chemotherapy in the locally advanced setting: occurrence of metastasis after 6 months from the last dose of chemotherapy;

  • For patients with adenocarcinoma: absence of HER2 expression;
  • Life expectancy >/=3 months as determined by the investigator;
  • Measurable disease per RECIST v1.1;
  • Adequate hematologic and end-organ function;
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs;
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm;
  • ECOG Performance Status of 0, 1, or 2.

Exclusion Criteria:

Exclusion criteria for the 2L Gastric Cancer Cohort:

  • Urinary protein is > 1 + on dipstick and the required following 24-hour urine collection shows urinary protein > 2000 mg;
  • Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to initiation of study treatment;
  • History of gastrointestinal perforation and/or fistulae within 6 months prior to initiation of study treatment;
  • Presence of a bowel obstruction, history or presence of inflammatory enteropathy, or extensive intestinal resection, Crohn disease, ulcerative colitis, or chronic diarrhea;
  • Uncontrolled arterial hypertension >/= 150/ >/= 90 millimeter of mercury (mmHg) despite standard medical management;
  • Chronic therapy with non-steroidal anti-inflammatory agents or other anti-platelet agents.

Gastric Cancer Exclusion Criteria:

  • Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy;
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases;
  • History of leptomeningeal disease;
  • Active or history of autoimmune disease or immune deficiency;
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan;
  • Positive test for human immunodeficiency virus (HIV) at screening;
  • Active hepatitis B virus (HBV) or hepatitis C (HCV) infection;
  • Severe infection within 4 weeks prior to initiation of study treatment;
  • Significant cardiovascular disease;
  • Significant bleeding disorder;
  • Prior allogeneic stem cell or solid organ transplantation;
  • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study;
  • Treatment with anticoagulation with warfarin, low-molecular-weight heparin, or similar agents for therapeutic purposes;
  • History of malignancy other than gastric or gastroesophageal junction carcinoma within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death;
  • Known allergy or hypersensitivity to any of the study drugs or their excipients.

Esophageal Cancer Cohort Exclusion Criteria:

  • High risk for developing esophageal fistula by clinical assessment or imaging;
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) Metastases;
  • Positive EBV viral capsid antigen IgM test at screening;
  • History of leptomeningeal disease;
  • Active or history of autoimmune disease or immune deficiency;
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan;
  • Active tuberculosis;
  • Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina;
  • History of malignancy other than esophageal cancer within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death;
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab or within 90 days after the final dose of tiragolumab.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 1L-Control: mFOLFOX6 (Gastric Cancer)
Participants in the 1L Gastric Cancer Control arm will receive modified FOLFOX6 (mFOLFOX6) treatment consisting of 5-fluorouracil (5-FU), leucovorin (folinic acid), and oxaliplatin. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria. No longer enrolling participants as of June 2018.
Drug: 5-Fluorouracil (5-FU)
5-FU 2400 milligrams per square meter (mg/m^2) by continuous intravenous (IV) infusion over 46 hours on Days 1 and 2 and Days 15 and 16 of every 28-day cycle.
Drug: Leucovorin
Leucovorin: 100 mg/m^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Folinic acid
Drug: Oxaliplatin
Oxaliplatin: 100 mg/m^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
Drug: 5-Fluorouracil (5-FU)
5-FU 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.
Experimental: 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)
Participants in the 1L-A Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab plus cobimetinib. No longer enrolling participants as of June 2018.
Drug: 5-Fluorouracil (5-FU)
5-FU 2400 milligrams per square meter (mg/m^2) by continuous intravenous (IV) infusion over 46 hours on Days 1 and 2 and Days 15 and 16 of every 28-day cycle.
Drug: Leucovorin
Leucovorin: 100 mg/m^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Folinic acid
Drug: Oxaliplatin
Oxaliplatin: 100 mg/m^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
Drug: 5-Fluorouracil (5-FU)
5-FU 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.
Drug: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Cobimetinib
Cobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle
Other Names:
  • Cotellic
Drug: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Names:
  • Tecentriq
Drug: Cobimetinib
Cobimetinib: 40 or 60 mg (depending on the recommended dose determined during the safety run-in phase) by mouth once a day on Days 1-21 of every 28-day cycle.
Other Names:
  • Cotellic
Experimental: 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)
Participants in the 1L-A2 Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab during cycles 1 and 2 followed by atezolizumab plus cobimetinib during cycles 3 and beyond. No longer enrolling participants as of June 2018.
Drug: 5-Fluorouracil (5-FU)
5-FU 2400 milligrams per square meter (mg/m^2) by continuous intravenous (IV) infusion over 46 hours on Days 1 and 2 and Days 15 and 16 of every 28-day cycle.
Drug: Leucovorin
Leucovorin: 100 mg/m^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Folinic acid
Drug: Oxaliplatin
Oxaliplatin: 100 mg/m^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
Drug: 5-Fluorouracil (5-FU)
5-FU 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.
Drug: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Cobimetinib
Cobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle
Other Names:
  • Cotellic
Drug: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Names:
  • Tecentriq
Drug: Cobimetinib
Cobimetinib: 40 or 60 mg (depending on the recommended dose determined during the safety run-in phase) by mouth once a day on Days 1-21 of every 28-day cycle.
Other Names:
  • Cotellic
Active Comparator: 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer)
Participants in the 2L Gastric Cancer Control arm received ramucirumab plus paclitaxel. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
Biological: Ramucirumab
Ramucirumab: 8 mg/kg administered by IV infusion over 60 minutes on Days 1 and 15 of every 28-day cycle.
Drug: Paclitaxel
Paclitaxel: 80 mg/m^2 administered by IV infusion on Days 1, 8, and 15 of every 28-day cycle.
Experimental: 2L-1: Atezo + Cobi (Gastric Cancer)
Participants in the 2L-1 Gastric Cancer arm received atezolizumab in combination with cobimetinib. Enrollment completed as of October 2019.
Drug: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Cobimetinib
Cobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle
Other Names:
  • Cotellic
Drug: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Names:
  • Tecentriq
Drug: Cobimetinib
Cobimetinib: 40 or 60 mg (depending on the recommended dose determined during the safety run-in phase) by mouth once a day on Days 1-21 of every 28-day cycle.
Other Names:
  • Cotellic
Experimental: 2L-2: Atezo + PEGPH20 (Gastric Cancer)
Participants in the 2L-2 Gastric Cancer arm received atezolizumab in combination with PEGylated recombinant human hyaluronidase (PEGPH20). Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
Drug: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Names:
  • Tecentriq
Biological: PEGylated recombinant human hyaluronidase (PEGPH20)
PEGPH20: 3 micrograms per kilogram (mcg/kg) administered by IV infusion on Days 1, 8, and 15 of every 21-day cycle.
Experimental: 2L-3: Atezo + BL-8040 (Gastric Cancer)
Participants in the 2L-3 Gastric Cancer arm received atezolizumab in combination with BL-8040. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
Drug: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Names:
  • Tecentriq
Drug: BL-8040
BL-8040: 1.25 mg/kg administered by subcutaneous (SC) injection on Days 1-5 during the 5-day priming period prior to Cycle 1; 1.25 mg/kg administered by SC injection three times a week (Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of every 21-day cycle).
Experimental: 2L-4: Atezo + Linagliptin (Gastric Cancer)
Participants in the 2L-4 Gastric Cancer arm received atezolizumab in combination with linagliptin. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
Drug: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Names:
  • Tecentriq
Drug: Linagliptin
Linagliptin: 5 mg orally once a day of every 21-day cycle.
Experimental: 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)
Participants in the 1L-1 Esophageal Cancer arm will receive atezolizumab in combination with tiragolumab and chemotherapy.
Drug: 5-Fluorouracil (5-FU)
5-FU 2400 milligrams per square meter (mg/m^2) by continuous intravenous (IV) infusion over 46 hours on Days 1 and 2 and Days 15 and 16 of every 28-day cycle.
Drug: 5-Fluorouracil (5-FU)
5-FU 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.
Drug: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Names:
  • Tecentriq
Drug: Cisplatin
Cisplatin: 80 mg/m^2 administered by IV infusion on Day 1 of each 21 day cycle. Treatment will be capped after 6 doses.
Drug: Tiragolumab
Tiragolumab: 600 mg administered by IV infusion on Day 1 of every 21 day cycle.
Other Names:
  • RO7092284
Experimental: 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort)
Participants in the 1L-2 Esophageal Cancer arm will receive atezolizumab in combination with chemotherapy.
Drug: 5-Fluorouracil (5-FU)
5-FU 2400 milligrams per square meter (mg/m^2) by continuous intravenous (IV) infusion over 46 hours on Days 1 and 2 and Days 15 and 16 of every 28-day cycle.
Drug: 5-Fluorouracil (5-FU)
5-FU 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.
Drug: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Names:
  • Tecentriq
Drug: Cisplatin
Cisplatin: 80 mg/m^2 administered by IV infusion on Day 1 of each 21 day cycle. Treatment will be capped after 6 doses.
Active Comparator: 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort)
Participants in the 1L-Control Eophageal Cancer arm will receive chemotherapy.
Drug: 5-Fluorouracil (5-FU)
5-FU 2400 milligrams per square meter (mg/m^2) by continuous intravenous (IV) infusion over 46 hours on Days 1 and 2 and Days 15 and 16 of every 28-day cycle.
Drug: 5-Fluorouracil (5-FU)
5-FU 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.
Drug: Cisplatin
Cisplatin: 80 mg/m^2 administered by IV infusion on Day 1 of each 21 day cycle. Treatment will be capped after 6 doses.
Experimental: 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort)
Participants in the 1L-3 Esophageal Cancer arm will receive atezolizumab + tiragolumab treatment. Participants from the cisplatin + 5-FU esophageal cancer cohort arm may be permitted to enroll in this arm if they progress after receiving chemotherapy.
Drug: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Names:
  • Tecentriq
Drug: Tiragolumab
Tiragolumab: 600 mg administered by IV infusion on Day 1 of every 21 day cycle.
Other Names:
  • RO7092284

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percentage of Participants With Objective Response, as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
Time Frame: From Randomization until disease progression or loss of clinical benefit (up to approximately 3-6 years)
From Randomization until disease progression or loss of clinical benefit (up to approximately 3-6 years)
Percentage of Participants with Adverse Events (AEs)
Time Frame: From first study treatment administration until 30 days after the last dose or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to approximately 3-6 years)
From first study treatment administration until 30 days after the last dose or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to approximately 3-6 years)
For Arm 1L-A : Percentage of Participants with Serious and Non-serious Treatment-related AEs
Time Frame: During the safety run-in phase up to 28 days
During the safety run-in phase up to 28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Are Alive at Month 6 and at Month 12
Time Frame: Month 6, Month 12
Month 6, Month 12
Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1
Time Frame: From randomization up to the first occurrence of disease (up to approximately 3-6 years)
From randomization up to the first occurrence of disease (up to approximately 3-6 years)
Overall Survival (OS)
Time Frame: From randomization up to death from any cause (up to approximately 3-6 years)
From randomization up to death from any cause (up to approximately 3-6 years)
Duration of Response, as Determined by Investigator According to RECIST v1.1
Time Frame: From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 3-6 years)
From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 3-6 years)
Percentage of Participants With Disease Control, as Determined by the Investigator per RECIST v1.1
Time Frame: From randomization until disease progression or loss of clinical benefit (up to approximately 3-6 years)
From randomization until disease progression or loss of clinical benefit (up to approximately 3-6 years)
Serum Concentration of Atezolizumab
Time Frame: Pre-infusion (0 hour [hr]), 30 minutes (min) post-infusion (infusion=60 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycles 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose (up to approximately 3-6 years)
Pre-infusion (0 hour [hr]), 30 minutes (min) post-infusion (infusion=60 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycles 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose (up to approximately 3-6 years)
Plasma Concentration of Cobimetinib
Time Frame: Prior to cobimetinib dose, 2-4 hr after cobimetinib dose on Day 15 of Cycle 1 (cycle length=28 days)
Prior to cobimetinib dose, 2-4 hr after cobimetinib dose on Day 15 of Cycle 1 (cycle length=28 days)
Plasma Concentration of PEGPH20
Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to 30 days and 120 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)
Pre-infusion (0 hr), 5 min and 1-3 hrs post infusion (infusion duration=10-12 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Days 8 and 15 of Cycle 1, Day 1 of Cycles 3, 4, 8, 12, 16; pre-infusion (0 hr) and 5 min post-infusion on Day 1 of Cycle 2 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-6 years)
Pre-infusion (0 hr) on Day 1 of Cycle 1 up to 30 days and 120 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)
Plasma Concentration of BL-8040
Time Frame: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)
Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1); 1 hr post-dose on Days 1, 5 of priming period; pre-dose (0 hr), 1 hour post-dose on Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16; pre-dose (0 hr) on Day 1 of Cycle 20 and every 4 cycles thereafter (each cycle=21 days) (up to approximately 3-6 years); 30 days after last dose (up to approximately 3-6 years)
Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)
Plasma Concentration of Linagliptin
Time Frame: 2 hr postdose oral linagliptin on Day 1 of Cycle 1, prior to atezolizumab infusion and predose oral linagliptin on Day 15 of Cycle 1 as well as on Day 1 of Cycles 2, 3, and 4
2 hr postdose oral linagliptin on Day 1 of Cycle 1, prior to atezolizumab infusion and predose oral linagliptin on Day 15 of Cycle 1 as well as on Day 1 of Cycles 2, 3, and 4
Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab
Time Frame: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose (up to approximately 3-6 years)
Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose (up to approximately 3-6 years)
Percentage of Participants With ADA to PEGPH20
Time Frame: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-6 years)
Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-6 years)
Percentage of Participants With ADA to BL-8040
Time Frame: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)
Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Cycle 1 Day 1), Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20 and every 4 cycles thereafter (each cycle=21 days) (up to approximately 3-6 years); 30 days after last dose (up to approximately 3-6 years)
Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
BioLineRx, Ltd.
Halozyme Therapeutics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 13, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 9, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 9, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 11, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 13, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 15, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • YO39609
  • 2016-004529-17 (EudraCT Number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

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