A Study of Nivolumab, Nivolumab Plus Ipilimumab, or Investigator's Choice Chemotherapy for the Treatment of Participants With Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) Metastatic Colorectal Cancer (mCRC)
Summary
The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS), Objective Response Rate (ORR), and Overall Survival (OS), achieved by nivolumab in combination with ipilimumab or by nivolumab monotherapy in participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) metastatic colorectal cancer (mCRC). This study will also compare nivolumab plus ipilimumab combination vs chemotherapy for treatment of MSI-H/dMMR mCRC participants.
Timeline
- Start
- 2019-08-05
- Primary completion
- 2024-08-28
- Completion
- 2026-06-10
Outcome
Met primary endpoint
registry analysis (superiority test); Arm A - Nivolumab Monotherapy vs Arm B - Nivolumab + Ipilimumab; p = 0.0003; Hazard Ratio (HR) 0.62 (95% CI 0.48 to 0.81) NCT04008030 ↗
registry analysis (superiority test); Arm B - Nivolumab + Ipilimumab vs Arm C - Investigator's Choice Chemotherapy; p <0.0001; Hazard Ratio (HR) 0.21 (95% CI 0.14 to 0.32) NCT04008030 ↗
Publications
- Andre T, Elez E, Lenz HJ, Jensen LH, Touchefeu Y, Van Cutsem E, Garcia-Carbonero R, Tougeron D, Mendez GA, Schenker M, de la Fouchardiere C, Limon ML, Yoshino T, Li J, Manzano Mozo JL, Dahan L, Tortora G, Chalabi M, Goekkurt E, Braghiroli MI, Joshi R, Cil T, Aubin F, Cela E, Chen T, Lei M, Jin L, Blum SI, Lonardi S. Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial. Lancet. 2025 Feb 1;405(10476):383-395. doi: 10.1016/S0140-6736(24)02848-4. Epub 2025 Jan 25.
- Andre T, Elez E, Van Cutsem E, Jensen LH, Bennouna J, Mendez G, Schenker M, de la Fouchardiere C, Limon ML, Yoshino T, Li J, Lenz HJ, Manzano Mozo JL, Tortora G, Garcia-Carbonero R, Dahan L, Chalabi M, Joshi R, Goekkurt E, Braghiroli MI, Cil T, Cela E, Chen T, Lei M, Dixon M, Abdullaev S, Lonardi S; CheckMate 8HW Investigators. Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer. N Engl J Med. 2024 Nov 28;391(21):2014-2026. doi: 10.1056/NEJMoa2402141.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Bevacizumab | Monoclonal antibody | — | — |
| Comparator | Cetuximab | Monoclonal antibody | — | — |
| Subject | Ipilimumab | Monoclonal antibody | 1 mg/kg | Intravenous |
| Comparator | Irinotecan | Small molecule | — | — |
| Comparator | Leucovorin | Small molecule | — | — |
| Subject | Nivolumab | Monoclonal antibody | 480 mg | Intravenous |
| Comparator | Oxaliplatin | Small molecule | — | — |
| Comparator | fluorouracil | Small molecule | — | — |