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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)
Sponsor: Hoffmann-La Roche
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.
Official title: 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)
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
219
Start Date
2017-10-13
Completion Date
2025-10-09
Last Updated
2026-08-03
Healthy Volunteers
No
Conditions
Interventions
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.
Leucovorin
Leucovorin: 100 mg/m\^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
Oxaliplatin
Oxaliplatin: 100 mg/m\^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Cobimetinib
Cobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle
Ramucirumab
Ramucirumab: 8 mg/kg administered by IV infusion over 60 minutes on Days 1 and 15 of every 28-day cycle.
Paclitaxel
Paclitaxel: 80 mg/m\^2 administered by IV infusion on Days 1, 8, and 15 of every 28-day cycle.
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.
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).
Linagliptin
Linagliptin: 5 mg orally once a day of every 21-day cycle.
Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
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.
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.
Tiragolumab
Tiragolumab: 600 mg administered by IV infusion on Day 1 of every 21 day cycle.
5-Fluorouracil (5-FU)
5-FU 800 mg/m\^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.
Locations (28)
Mayo Clinic Cancer Center
Scottsdale, Arizona, United States
Uni of Southern California
Los Angeles, California, United States
UCLA Jonsson Comprehensive Cancer Center
Santa Monica, California, United States
Columbia University Medical Center
New York, New York, United States
Tennessee Oncology - Nashville
Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Blacktown Hospital
Blacktown, New South Wales, Australia
Monash Medical Centre-Moorabbin Campus
Clayton, Victoria, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Rambam Health Care Campus
Haifa, Israel
Sourasky Medical Centre
Tel Aviv, Israel
Seoul National University Bundang Hospital
Gyeonggi-do, South Korea
Korea University Anam Hospital
Seoul, South Korea
Seoul National University Hospital
Seoul, South Korea
Samsung Medical Center
Seoul, 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, South Korea
The Catholic University of Korea St. Vincent's Hospital
Suwon, South Korea
Universidad de Navarra - Clinica Universitaria de Navarra (CUN)
Pamplona, Navarre, Spain
Hospital Universitari Vall dHebron
Barcelona, Spain
National Cheng Kung University Hospital
Tainan, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Barts and The London School of Medicine and Dentistry - Barts Cancer Institute (BCI)-CECM
London, United Kingdom
The Royal Marsden
London, United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom
The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH) - Sutton
Sutton, United Kingdom