CheckMate 067
Phase 3 Study of Nivolumab or Nivolumab Plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma (CheckMate 067)
Phase 3N = 945NCT01844505
- Population
- Previously untreated unresectable stage III or IV melanoma
- Design
- Double-blind randomised (1:1:1) phase 3 trial of nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone in untreated advanced melanoma; randomisation stratified by PD-L1 status, BRAF mutation status and metastasis stage. Progression-free survival and overall survival were co-primary end points. The primary paper states the trial was not designed for a formal statistical comparison between the nivolumab-alone and nivolumab-plus-ipilimumab groups (full text, PMC5698905).
- Primary endpoint
- PFS, OS
- Arms
- Nivolumab plus ipilimumab (experimental, n = 314): Nivolumab 1 mg per kilogram plus ipilimumab 3 mg per kilogram every 3 weeks for four doses, then nivolumab 3 mg per kilogram every 2 weeks
- Nivolumab (experimental, n = 316): Nivolumab 3 mg per kilogram every 2 weeks plus placebo
- Ipilimumab (control, n = 315): Ipilimumab 3 mg per kilogram every 3 weeks for four doses plus placebo
- People
- Larkin J, senior author Wolchok JD
PFSHR 0.42Δ median PFS+8.6 monthsPFSHR 0.57Δ median PFS+4 monthsΔ ORR+38.6 pointsOSHR 0.55
Show the numbers
| Endpoint | Analysis | Nivolumab plus ipilimumab / Nivolumab | Ipilimumab | Effect |
|---|---|---|---|---|
| PFSRandomised population as described in the abstract (analysis population not stated there) | primaryLarkin 2015 | median 11.5 months (8.9–16.7) | median 2.9 months (2.8–3.4) | HR 0.42P<0.001Hazard ratio for death or disease progression with a 99.5% confidence interval of 0.31 to 0.57, as published. |
| PFSRandomised population as described in the abstract (analysis population not stated there) | primaryLarkin 2015 | median 6.9 months (4.3–9.5) | median 2.9 months (2.8–3.4) | HR 0.57P<0.001Hazard ratio versus ipilimumab with a 99.5% confidence interval of 0.43 to 0.76, as published. |
| ORRRandomised patients (945) as described in the full text | primaryLarkin 2015 | 57.6% (52.0–63.2%) | 19% (14.9–23.8%) | Investigator-assessed objective response rate as printed in the full text; read from the PubMed Central author manuscript. The response rate is not in the abstract. |
| OSRandomised population as described in the abstract (analysis population not stated there) | long term-updateWolchok 2017 | 58% at 3 y | median 19.9 months; 34% at 3 y | HR 0.55P<0.001Minimum follow-up 36 months. Median overall survival was not reached with nivolumab plus ipilimumab. |
| OSRandomised population as described in the abstract (analysis population not stated there) | long term-updateWolchok 2017 | median 37.6 months; 52% at 3 y | median 19.9 months; 34% at 3 y | HR 0.65P<0.001Minimum follow-up 36 months. |
| OSIntention-to-treat population (full text, Figure 1 legend) | finalWolchok 2025 | median 71.9 months (38.2–114.4) | median 19.9 months (16.8–24.6) | HR 0.53 (95% CI 0.44–0.65)Minimum follow-up of 10 years. |
| OSIntention-to-treat population (full text, Figure 1 legend) | finalWolchok 2025 | median 36.9 months (28.2–58.7) | median 19.9 months (16.8–24.6) | HR 0.63 (95% CI 0.52–0.76)Minimum follow-up of 10 years. |
| OSIntention-to-treat population (full text, Figure 1 legend) | finalWolchok 2025 | 43% at 10 y | 19% at 10 y | Ten-year overall survival rates as printed in the Results (Survival Outcomes) of the open-access full text; no confidence intervals were read for the rates. |
| Endpoint | Analysis | Nivolumab plus ipilimumab / Nivolumab | Ipilimumab | Effect |
|---|---|---|---|---|
| PFSRandomised population as described in the abstract (analysis population not stated there) | primaryLarkin 2015 | median 11.5 months (8.9–16.7) | median 2.9 months (2.8–3.4) | HR 0.42P<0.001Hazard ratio for death or disease progression with a 99.5% confidence interval of 0.31 to 0.57, as published. |
| PFSRandomised population as described in the abstract (analysis population not stated there) | primaryLarkin 2015 | median 6.9 months (4.3–9.5) | median 2.9 months (2.8–3.4) | HR 0.57P<0.001Hazard ratio versus ipilimumab with a 99.5% confidence interval of 0.43 to 0.76, as published. |
| ORRRandomised patients (945) as described in the full text | primaryLarkin 2015 | 57.6% (52.0–63.2%) | 19% (14.9–23.8%) | Investigator-assessed objective response rate as printed in the full text; read from the PubMed Central author manuscript. The response rate is not in the abstract. |
| OSRandomised population as described in the abstract (analysis population not stated there) | long term-updateWolchok 2017 | 58% at 3 y | median 19.9 months; 34% at 3 y | HR 0.55P<0.001Minimum follow-up 36 months. Median overall survival was not reached with nivolumab plus ipilimumab. |
| OSRandomised population as described in the abstract (analysis population not stated there) | long term-updateWolchok 2017 | median 37.6 months; 52% at 3 y | median 19.9 months; 34% at 3 y | HR 0.65P<0.001Minimum follow-up 36 months. |
| OSIntention-to-treat population (full text, Figure 1 legend) | finalWolchok 2025 | median 71.9 months (38.2–114.4) | median 19.9 months (16.8–24.6) | HR 0.53 (95% CI 0.44–0.65)Minimum follow-up of 10 years. |
| OSIntention-to-treat population (full text, Figure 1 legend) | finalWolchok 2025 | median 36.9 months (28.2–58.7) | median 19.9 months (16.8–24.6) | HR 0.63 (95% CI 0.52–0.76)Minimum follow-up of 10 years. |
| OSIntention-to-treat population (full text, Figure 1 legend) | finalWolchok 2025 | 43% at 10 y | 19% at 10 y | Ten-year overall survival rates as printed in the Results (Survival Outcomes) of the open-access full text; no confidence intervals were read for the rates. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.53 | 0.44–0.65 |
| OS | 0.63 | 0.52–0.76 |
- Nivolumab plus ipilimumab (experimental)
- Ipilimumab (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Nivolumab plus ipilimumab | Ipilimumab |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 7 | 65.6% | 18.8% |
| 14 | 43.0% | 3.5% |
| 22 | 26.6% | 0.5% |
| 29 | 17.4% | 0.1% |
- Nivolumab (experimental)
- Ipilimumab (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 |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 4 | 66.9% | 38.4% |
| 9 | 40.5% | 11.6% |
| 13 | 27.1% | 4.5% |
| 17 | 18.1% | 1.7% |
Appears in
Sources
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(1):23-34.
Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017;377(14):1345-1356.
Wolchok JD, Chiarion-Sileni V, Rutkowski P, Cowey CL, Schadendorf D, Wagstaff J, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. 2025;392(1):11-22.