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)

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.

Conditions

• Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma

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.

Sponsors & Collaborators

• Halozyme Therapeutics

  collaborator INDUSTRY

• BioLineRx, Ltd.

  collaborator INDUSTRY

• Hoffmann-La Roche

  lead INDUSTRY

Principal Investigators

• Clinical Trials · Hoffmann-La Roche

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-10-13

Primary Completion

2025-10-09

Completion

2025-10-09

FDA Drug

Yes

Countries

• United States
• Australia
• Israel
• South Korea
• Spain
• Taiwan
• United Kingdom

Study Locations