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)
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)
2 other identifiers
interventional
214
7 countries
28
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2017
Longer than P75 for phase_1
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 11, 2017
CompletedFirst Posted
Study publicly available on registry
September 13, 2017
CompletedStudy Start
First participant enrolled
October 13, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 9, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
October 9, 2025
CompletedDecember 15, 2025
December 1, 2025
8 years
September 11, 2017
December 9, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
Percentage of Participants With Objective Response, as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
From Randomization until disease progression or loss of clinical benefit (up to approximately 3-6 years)
Percentage of Participants with Adverse Events (AEs)
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
During the safety run-in phase up to 28 days
Secondary Outcomes (13)
Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1
From randomization up to the first occurrence of disease (up to approximately 3-6 years)
Overall Survival (OS)
From randomization up to death from any cause (up to approximately 3-6 years)
Percentage of Participants Who Are Alive at Month 6 and at Month 12
Month 6, Month 12
Duration of Response, as Determined by Investigator According to RECIST v1.1
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
From randomization until disease progression or loss of clinical benefit (up to approximately 3-6 years)
- +8 more secondary outcomes
Study Arms (12)
1L-Control: mFOLFOX6 (Gastric Cancer)
ACTIVE COMPARATORParticipants 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.
1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)
EXPERIMENTALParticipants 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.
1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)
EXPERIMENTALParticipants 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.
2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer)
ACTIVE COMPARATORParticipants 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.
2L-1: Atezo + Cobi (Gastric Cancer)
EXPERIMENTALParticipants in the 2L-1 Gastric Cancer arm received atezolizumab in combination with cobimetinib. Enrollment completed as of October 2019.
2L-2: Atezo + PEGPH20 (Gastric Cancer)
EXPERIMENTALParticipants 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.
2L-3: Atezo + BL-8040 (Gastric Cancer)
EXPERIMENTALParticipants 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.
2L-4: Atezo + Linagliptin (Gastric Cancer)
EXPERIMENTALParticipants 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.
1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)
EXPERIMENTALParticipants in the 1L-1 Esophageal Cancer arm will receive atezolizumab in combination with tiragolumab and chemotherapy.
1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort)
EXPERIMENTALParticipants in the 1L-2 Esophageal Cancer arm will receive atezolizumab in combination with chemotherapy.
1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort)
ACTIVE COMPARATORParticipants in the 1L-Control Eophageal Cancer arm will receive chemotherapy.
1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort)
EXPERIMENTALParticipants 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.
Interventions
Leucovorin: 100 mg/m\^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
Oxaliplatin: 100 mg/m\^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
Ramucirumab: 8 mg/kg administered by IV infusion over 60 minutes on Days 1 and 15 of every 28-day cycle.
Paclitaxel: 80 mg/m\^2 administered by IV infusion on Days 1, 8, and 15 of every 28-day cycle.
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).
Linagliptin: 5 mg orally once a day of every 21-day cycle.
PEGPH20: 3 micrograms per kilogram (mcg/kg) administered by IV infusion on Days 1, 8, and 15 of every 21-day cycle.
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Cobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle
Cisplatin: 80 mg/m\^2 administered by IV infusion on Day 1 of each 21 day cycle. Treatment will be capped after 6 doses.
Tiragolumab: 600 mg administered by IV infusion on Day 1 of every 21 day cycle.
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.
Eligibility Criteria
You may qualify if:
- 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.
- 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;
- +5 more criteria
You may not qualify if:
- 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.
- 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;
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Hoffmann-La Rochelead
- Halozyme Therapeuticscollaborator
- BioLineRx, Ltd.collaborator
Study Sites (28)
Mayo Clinic Cancer Center
Scottsdale, Arizona, 85259, United States
Uni of Southern California
Los Angeles, California, 90033, United States
UCLA Jonsson Comprehensive Cancer Center
Santa Monica, California, 90404, United States
Columbia University Medical Center
New York, New York, 10032, United States
Tennessee Oncology - Nashville
Nashville, Tennessee, 37203, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4000, United States
Blacktown Hospital
Blacktown, New South Wales, 2148, Australia
Monash Medical Centre-Moorabbin Campus
Clayton, Victoria, 3168, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
Rambam Health Care Campus
Haifa, 3109601, Israel
Sourasky Medical Centre
Tel Aviv, 64239, Israel
Seoul National University Bundang Hospital
Gyeonggi-do, 13620, South Korea
Korea University Anam Hospital
Seoul, 02841, South Korea
Seoul National University Hospital (SNUH) - Medical Oncology Center
Seoul, 03080, South Korea
Samsung Medical Center
Seoul, 135-710, South Korea
Yonsei University College of Medicine (YUCM)-Yonsei Cancer Center
Seoul, South Korea
University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC)
Songpa-gu, 05505, South Korea
The Catholic University of Korea St. Vincent's Hospital
Suwon, 442-723, South Korea
Universidad de Navarra - Clinica Universitaria de Navarra (CUN)
Pamplona, Navarre, 31008, Spain
Hospital Universitari Vall dHebron
Barcelona, 08035, Spain
National Cheng Kung University Hospital
Tainan, 70457, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
National Taiwan University Hospital (NTUH) - Cancer Research Center
Zhongzheng Dist., 10051, Taiwan
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
Barts and The London School of Medicine and Dentistry - Barts Cancer Institute (BCI)-CECM
London, 0, United Kingdom
The Royal Marsden
London, SW7 3RP, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH) - Sutton
Sutton, SM2 5PT, United Kingdom
Related Publications (2)
Sun JM, Chao Y, Kim SB, Rha SY, Evans TRJ, Strickland AH, Wainberg Z, Chau I, Pelles-Avraham S, Ajani J, Malhotra R, Liu Q, Li S, Cha E, Kalaitzidou M, Huang X, Allen S, Hsu CH. First-line tiragolumab plus atezolizumab and chemotherapy in patients with previously untreated, locally advanced unresectable or metastatic oesophageal cancer (MORPHEUS-EC): a randomised, open-label, phase 1b/2 trial. Lancet Oncol. 2026 Jan;27(1):90-102. doi: 10.1016/S1470-2045(25)00402-4.
PMID: 41449151DERIVEDKo AH, Kim KP, Siveke JT, Lopez CD, Lacy J, O'Reilly EM, Macarulla T, Manji GA, Lee J, Ajani J, Alsina Maqueda M, Rha SY, Lau J, Al-Sakaff N, Allen S, Lu D, Shemesh CS, Gan X, Cha E, Oh DY. Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform. Oncologist. 2023 Jun 2;28(6):553-e472. doi: 10.1093/oncolo/oyad022.
PMID: 36940261DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
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
September 11, 2017
First Posted
September 13, 2017
Study Start
October 13, 2017
Primary Completion
October 9, 2025
Study Completion
October 9, 2025
Last Updated
December 15, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
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