CheckMate 8HW
A Phase 3 Randomized Clinical Trial of Nivolumab Alone, Nivolumab in Combination With Ipilimumab, or Investigator's Choice Chemotherapy in Participants With Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) Metastatic Colorectal Cancer
Phase 3NCT04008030
- Population
- Unresectable or metastatic colorectal cancer with MSI-H or dMMR status by local testing; the first-line comparison enrolled patients with no previous systemic treatment for metastatic disease
- Design
- Open-label, international phase 3 trial (128 hospitals in 23 countries per the Lancet report) with 2:2:1 randomisation to nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies, in immunotherapy-naive adults with MSI-H or dMMR status by local testing. Dual primary endpoints, assessed in patients with centrally confirmed MSI-H or dMMR status: progression-free survival with nivolumab plus ipilimumab versus chemotherapy as first-line therapy (NEJM 2024) and progression-free survival with nivolumab plus ipilimumab versus nivolumab alone across all treatment lines (Lancet 2025).
- Primary endpoint
- PFS
- Arms
- Chemotherapy (control): Investigator's choice of chemotherapy with or without targeted therapies
- Nivolumab (control, n = 353): Nivolumab 240 mg every 2 weeks for six doses, then 480 mg every 4 weeks
- Nivolumab + ipilimumab (experimental, n = 354): Nivolumab 240 mg plus ipilimumab 1 mg/kg every 3 weeks for four doses, then nivolumab 480 mg every 4 weeks
- People
- Andre T
Δ 24-month PFS+58 pointsPFSHR 0.62 (95% CI 0.48–0.81)
Show the numbers
| Endpoint | Analysis | Nivolumab + ipilimumab | Chemotherapy / Nivolumab | Effect |
|---|---|---|---|---|
| PFSFirst line, centrally confirmed MSI-H or dMMR status (255 of the 303 patients randomised to these two arms)Progression-free survival, nivolumab + ipilimumab versus chemotherapy, first line (first dual primary endpoint) | primarymedian follow-up 31.5 monthsAndre 2024 | 72% at 2 y (64–79%) | 14% at 2 y (6–25%) | P<0.001Reported in the NEJM 2024 paper. The abstract gives no hazard ratio or median PFS (full text not opened). At 24 months the restricted mean survival time was 10.6 months (95% CI 8.4 to 12.9) longer with nivolumab plus ipilimumab. P value from a two-sided stratified log-rank test. |
| PFSAll treatment lines, centrally confirmed MSI-H or dMMR status (296 of 354 and 286 of 353 randomised patients)Progression-free survival by blinded independent central review, nivolumab + ipilimumab versus nivolumab, all treatment lines (second dual primary endpoint) | primarymedian follow-up 47 monthsAndré 2025 | — | median 39.3 months | HR 0.62 (95% CI 0.48–0.81)P=0.0003Reported in the Lancet 2025 paper (a separate publication from the NEJM first-line comparison). Median PFS was not reached with nivolumab plus ipilimumab (95% CI 53.8 to not estimable) and was 39.3 months with nivolumab (95% CI 22.1 to not estimable); medians with an open upper bound cannot be shown as intervals here. Median follow-up 47.0 months (IQR 38.4 to 53.2). |
| Endpoint | Analysis | Nivolumab + ipilimumab | Chemotherapy / Nivolumab | Effect |
|---|---|---|---|---|
| PFSFirst line, centrally confirmed MSI-H or dMMR status (255 of the 303 patients randomised to these two arms)Progression-free survival, nivolumab + ipilimumab versus chemotherapy, first line (first dual primary endpoint) | primarymedian follow-up 31.5 monthsAndre 2024 | 72% at 2 y (64–79%) | 14% at 2 y (6–25%) | P<0.001Reported in the NEJM 2024 paper. The abstract gives no hazard ratio or median PFS (full text not opened). At 24 months the restricted mean survival time was 10.6 months (95% CI 8.4 to 12.9) longer with nivolumab plus ipilimumab. P value from a two-sided stratified log-rank test. |
| PFSAll treatment lines, centrally confirmed MSI-H or dMMR status (296 of 354 and 286 of 353 randomised patients)Progression-free survival by blinded independent central review, nivolumab + ipilimumab versus nivolumab, all treatment lines (second dual primary endpoint) | primarymedian follow-up 47 monthsAndré 2025 | — | median 39.3 months | HR 0.62 (95% CI 0.48–0.81)P=0.0003Reported in the Lancet 2025 paper (a separate publication from the NEJM first-line comparison). Median PFS was not reached with nivolumab plus ipilimumab (95% CI 53.8 to not estimable) and was 39.3 months with nivolumab (95% CI 22.1 to not estimable); medians with an open upper bound cannot be shown as intervals here. Median follow-up 47.0 months (IQR 38.4 to 53.2). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.62 | 0.48–0.81 |
- Nivolumab (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Nivolumab |
|---|---|
| 0 | 100.0% |
| 25 | 64.3% |
| 49 | 42.1% |
| 74 | 27.1% |
| 98 | 17.8% |
Appears in
Sources
Andre T, Elez E, Van Cutsem E, Jensen LH, Bennouna J, Mendez G, et al. Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer. N Engl J Med. 2024;391(21):2014-2026.
André T, Elez E, Lenz HJ, Jensen LH, Touchefeu Y, Van Cutsem E, et al. Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial. Lancet. 2025;405(10476):383-395.