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)

Conditions

• Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• 5-Fluorouracil (5-FU) — DRUG
  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 — DRUG
  Leucovorin: 100 mg/m\^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
• Oxaliplatin — DRUG
  Oxaliplatin: 100 mg/m\^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
• Atezolizumab — DRUG
  Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
• Cobimetinib — DRUG
  Cobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle
• Ramucirumab — BIOLOGICAL
  Ramucirumab: 8 mg/kg administered by IV infusion over 60 minutes on Days 1 and 15 of every 28-day cycle.
• Paclitaxel — DRUG
  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) — BIOLOGICAL
  PEGPH20: 3 micrograms per kilogram (mcg/kg) administered by IV infusion on Days 1, 8, and 15 of every 21-day cycle.
• BL-8040 — DRUG
  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 — DRUG
  Linagliptin: 5 mg orally once a day of every 21-day cycle.
• Atezolizumab — DRUG
  Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
• Cobimetinib — DRUG
  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 — DRUG
  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 — DRUG
  Tiragolumab: 600 mg administered by IV infusion on Day 1 of every 21 day cycle.
• 5-Fluorouracil (5-FU) — DRUG
  5-FU 800 mg/m\^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.

Study Details

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.

Key Dates

Start date

Oct 13, 2017

Status verified

Dec 2025

Primary completion

Oct 9, 2025

Completion

Oct 9, 2025

Study Design

Enrollment

214 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Active Comparator: 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort)
  Participants in the 1L-Control Eophageal Cancer arm will receive chemotherapy.
• 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.

Primary Outcome Measure

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) ]

Locations (6)

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