CheckMate 238
Needs reviewAdjuvant nivolumab versus ipilimumab in resected stage IIIB, IIIC or IV melanoma
Phase 3N = 906NCT02388906
- Population
- Patients aged 15 years or older undergoing complete resection of stage IIIB, IIIC or IV melanoma
- Design
- Randomised, double-blind phase 3 trial, 1:1. Nivolumab or ipilimumab given for up to 1 year or until recurrence, unacceptable toxicity or withdrawal of consent. Randomisation was stratified by disease stage and PD-L1 status (9-year report). Primary endpoint recurrence-free survival.
- Primary endpoint
- RFS
- Arms
- Nivolumab (experimental, n = 453): Nivolumab 3 mg/kg intravenously every 2 weeks, up to 1 year
- Ipilimumab 10 mg/kg (control, n = 453): Ipilimumab 10 mg/kg intravenously every 3 weeks for four doses, then every 12 weeks, up to 1 year
- People
- Weber J, senior author Ascierto PA
RFSHR 0.65Δ 12-month RFS+9.7 pointsRFSHR 0.76 (95% CI 0.63–0.90)Δ median RFS+36.9 monthsΔ 108-month RFS+7 pointsDMFSHR 0.81 (95% CI 0.65–1.00)
Show the numbers
| Endpoint | Analysis | Nivolumab | Ipilimumab 10 mg/kg | Effect |
|---|---|---|---|---|
| RFS | primaryWeber 2017 | 70.5% at 12 mo (66.1–74.5%) | 60.8% at 12 mo (56.0–65.2%) | HR 0.65P<0.001Minimum follow-up 18 months. Hazard ratio for disease recurrence or death 0.65 with a 97.56% confidence interval of 0.51 to 0.83 (not a 95% interval). Treatment-related grade 3 or 4 adverse events 14.4% with nivolumab vs 45.9% with ipilimumab; discontinuation for any adverse event 9.7% vs 42.6%; two treatment-related deaths (0.4%) in the ipilimumab group. |
| RFSAll randomised patients (the abstract does not name the analysis population) | finalAscierto 2026 | median 61.1 months; 44% at 9 y | median 24.2 months; 37% at 9 y | HR 0.76 (95% CI 0.63–0.90)Minimum follow-up 107 months ('nearly 9 years'). 9-year RFS 44% vs 37% as published (no interval given in the abstract). The abstract calls these '9-year final data'. |
| DMFSPatients with stage III melanoma | long term-updateAscierto 2026 | 54% at 9 y | median 83.8 months; 48% at 9 y | HR 0.81 (95% CI 0.65–1.00)Median distant metastasis-free survival with nivolumab was reported as 'more than 9 years' (no value). Secondary endpoint; stage III patients only. |
| OSAll randomised patients (the abstract does not name the analysis population) | long term-updateAscierto 2026 | 69% at 9 y | 65% at 9 y | HR 0.88Hazard ratio for death 0.88 with a 95.03% confidence interval of 0.69 to 1.11. Median overall survival was more than 9 years in both groups (no value). Death from melanoma at 9 years 26% vs 30% (HR 0.87; 95% CI 0.67 to 1.13). Subsequent systemic therapy 37.3% (nivolumab) vs 44.6% (ipilimumab). Secondary endpoint. |
| Endpoint | Analysis | Nivolumab | Ipilimumab 10 mg/kg | Effect |
|---|---|---|---|---|
| RFS | primaryWeber 2017 | 70.5% at 12 mo (66.1–74.5%) | 60.8% at 12 mo (56.0–65.2%) | HR 0.65P<0.001Minimum follow-up 18 months. Hazard ratio for disease recurrence or death 0.65 with a 97.56% confidence interval of 0.51 to 0.83 (not a 95% interval). Treatment-related grade 3 or 4 adverse events 14.4% with nivolumab vs 45.9% with ipilimumab; discontinuation for any adverse event 9.7% vs 42.6%; two treatment-related deaths (0.4%) in the ipilimumab group. |
| RFSAll randomised patients (the abstract does not name the analysis population) | finalAscierto 2026 | median 61.1 months; 44% at 9 y | median 24.2 months; 37% at 9 y | HR 0.76 (95% CI 0.63–0.90)Minimum follow-up 107 months ('nearly 9 years'). 9-year RFS 44% vs 37% as published (no interval given in the abstract). The abstract calls these '9-year final data'. |
| DMFSPatients with stage III melanoma | long term-updateAscierto 2026 | 54% at 9 y | median 83.8 months; 48% at 9 y | HR 0.81 (95% CI 0.65–1.00)Median distant metastasis-free survival with nivolumab was reported as 'more than 9 years' (no value). Secondary endpoint; stage III patients only. |
| OSAll randomised patients (the abstract does not name the analysis population) | long term-updateAscierto 2026 | 69% at 9 y | 65% at 9 y | HR 0.88Hazard ratio for death 0.88 with a 95.03% confidence interval of 0.69 to 1.11. Median overall survival was more than 9 years in both groups (no value). Death from melanoma at 9 years 26% vs 30% (HR 0.87; 95% CI 0.67 to 1.13). Subsequent systemic therapy 37.3% (nivolumab) vs 44.6% (ipilimumab). Secondary endpoint. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| RFS | 0.76 | 0.63–0.9 |
| DMFS | 0.81 | 0.65–1 |
- Nivolumab (experimental)
- Ipilimumab 10 mg/kg (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Nivolumab | Ipilimumab 10 mg/kg |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 38 | 65.0% | 33.7% |
| 76 | 42.2% | 11.3% |
| 115 | 27.1% | 3.7% |
| 153 | 17.6% | 1.2% |
- Ipilimumab 10 mg/kg (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Ipilimumab 10 mg/kg |
|---|---|
| 0 | 100.0% |
| 52 | 65.0% |
| 105 | 42.0% |
| 157 | 27.3% |
| 210 | 17.6% |
Appears in
Sources
Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med. 2017;377(19):1824-1835.
Ascierto PA, Del Vecchio M, Merelli B, Gogas H, Arance AM, Dalle S, et al. Nivolumab for Resected Stage III or IV Melanoma at 9 Years. N Engl J Med. 2026;394(4):333-342.