MORPHEUS YO39609: This phase I/II trial is assessing how safe and tolerable a variety of immunotherapy-based treatment combinations are in people with locally advanced unresectable or metastatic gastric or gastroesophageal junction cancer, or esophageal cancerA 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)

Summary

This is a randomised trial with different cohorts and treatment arms. Corhorts include: 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. Participants in the 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort) Experimental Arm will receive atezolizumab in combination with tiragolumab and chemotherapy (intravenously): Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-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, and 5-Fluorouracil (5-FU) 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle. Participants in the 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort) Experimental Arm will receive atezolizumab in combination with chemotherapy (intravenously): Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-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, and 5-Fluorouracil (5-FU) 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle. Participants in the 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort) Active Comparator Arm will receive chemotherapy (intravenously): Cisplatin: 80 mg/m^2 administered by IV infusion on Day 1 of each 21 day cycle. Treatment will be capped after 6 doses and 5-Fluorouracil (5-FU) 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle. Participants in the 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort) Experimental Arm will receive atezolizumab + tiragolumab treatment (intravenuosly): Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle and Tiragolumab: 600 mg administered by IV infusion on Day 1 of every 21 day cycle. Participants from the cisplatin + 5-FU esophageal cancer cohort arm may be permitted to enroll in this arm if they progress after receiving chemotherapy. The following arms are no longer enrolling participants (as at July 2021): 1L-Control: mFOLFOX6 (Gastric Cancer), 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer),1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer), 1L-B: mFOLFOX6 + Atezo (Gastric Cancer), 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer), 2L-1: Atezo + Cobi (Gastric Cancer), 2L-2: Atezo + PEGPH20 (Gastric Cancer), 2L-3: Atezo + BL-8040 (Gastric Cancer), 2L-4: Atezo + Linagliptin (Gastric Cancer).

Treatment Type

Radiotherapy