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TERMINATED
NCT03281369
PHASE1/PHASE2

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

View on ClinicalTrials.gov

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

Interventions

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.

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

Atezolizumab

Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.

DRUG

Cobimetinib

Cobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle

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.

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.

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).

DRUG

Linagliptin

Linagliptin: 5 mg orally once a day of every 21-day cycle.

DRUG

Atezolizumab

Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle

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.

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.

DRUG

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