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.
Timeline
- Start
- 2017-10-13
- Primary completion
- 2025-10-09
- Completion
- 2025-10-09
Publications
- Sun JM, Chao Y, Kim SB, Rha SY, Evans TRJ, Strickland AH, Wainberg Z, Chau I, Pelles-Avraham S, Ajani J, Malhotra R, Liu Q, Li S, Cha E, Kalaitzidou M, Huang X, Allen S, Hsu CH. First-line tiragolumab plus atezolizumab and chemotherapy in patients with previously untreated, locally advanced unresectable or metastatic oesophageal cancer (MORPHEUS-EC): a randomised, open-label, phase 1b/2 trial. Lancet Oncol. 2026 Jan;27(1):90-102. doi: 10.1016/S1470-2045(25)00402-4.
- Ko AH, Kim KP, Siveke JT, Lopez CD, Lacy J, O'Reilly EM, Macarulla T, Manji GA, Lee J, Ajani J, Alsina Maqueda M, Rha SY, Lau J, Al-Sakaff N, Allen S, Lu D, Shemesh CS, Gan X, Cha E, Oh DY. Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform. Oncologist. 2023 Jun 2;28(6):553-e472. doi: 10.1093/oncolo/oyad022.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Atezolizumab | Monoclonal antibody | 840 mg | Intravenous |
| Subject | Atezolizumab | Monoclonal antibody | 1200 mg | Intravenous |
| Subject | Cisplatin | Other / unclassified | 80 mg/m2 | Intravenous |
| Subject | Cobimetinib | Small molecule | 40 mg | Oral |
| Subject | Cobimetinib | Small molecule | 60 mg | Oral |
| Subject | Leucovorin | Small molecule | 100 mg/m2 | Intravenous |
| Subject | Linagliptin | Small molecule | 5 mg | Oral |
| Subject | Motixafortide | Peptide | 1.25 mg/kg | Subcutaneous |
| Subject | Oxaliplatin | Small molecule | 100 mg/m2 | Intravenous |
| Subject | PEGylated Recombinant Human Hyaluronidase (PEGPH20) | Protein / enzyme biologic | 3 ug/kg | Intravenous |
| Comparator | Paclitaxel | Small molecule | 80 mg/m2 | Intravenous |
| Comparator | Ramucirumab | Monoclonal antibody | 8 mg/kg | Intravenous |
| Subject | Tiragolumab | Monoclonal antibody | 600 mg | Intravenous |
| Subject | fluorouracil | Small molecule | 800 mg/m2 | Intravenous |
| Subject | fluorouracil | Small molecule | 2400 mg/m2 | Intravenous |