CheckMate 214
Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)
Phase 3N = 1,096NCT02231749
- Population
- Adults with previously untreated advanced clear-cell renal-cell carcinoma
- Design
- Randomised (1:1), open-label phase 3 trial of nivolumab plus ipilimumab followed by nivolumab versus sunitinib, stratified by IMDC risk score and geographic region. The co-primary end points (overall survival, objective response rate, progression-free survival) were assessed in patients at intermediate or poor prognostic risk (425 and 422 patients); intention-to-treat and favourable-risk analyses were secondary and exploratory. A November 2017 protocol amendment, after the primary end point had been met, permitted crossover from sunitinib to nivolumab plus ipilimumab (full text).
- Primary endpoint
- OS, ORR, PFS
- Arms
- Nivolumab plus ipilimumab (experimental, n = 550): Nivolumab 3 mg per kilogram plus ipilimumab 1 mg per kilogram intravenously every 3 weeks for four doses, then nivolumab 3 mg per kilogram every 2 weeks
- Sunitinib (control, n = 546): Sunitinib 50 mg orally once daily for 4 weeks of each 6-week cycle
- People
- Motzer RJ, CheckMate 214 Investigators
OSHR 0.63Δ 18-month OS+15 pointsΔ ORR+15 pointsPFSHR 0.82Δ median PFS+3.2 monthsOSHR 0.68
Show the numbers
| Endpoint | Analysis | Nivolumab plus ipilimumab | Sunitinib | Effect |
|---|---|---|---|---|
| OSIntermediate- and poor-risk patients (425 nivolumab plus ipilimumab, 422 sunitinib) | primarymedian follow-up 25.2 monthsMotzer 2018 | 75% at 18 mo (70–78%) | median 26 months; 60% at 18 mo (55–65%) | HR 0.63P<0.001Hazard ratio for death with a 99.8% confidence interval of 0.44 to 0.89 (full text); the interval is not a 95% interval. Median overall survival was not reached with nivolumab plus ipilimumab. |
| ORRIntermediate- and poor-risk patients (425 nivolumab plus ipilimumab, 422 sunitinib) | primarymedian follow-up 25.2 monthsMotzer 2018 | 42% (37–47%) | 27% (22–31%) | P<0.001Complete responses occurred in 40 patients (9%) with nivolumab plus ipilimumab and 5 patients (1%) with sunitinib. |
| PFSIntermediate- and poor-risk patients (425 nivolumab plus ipilimumab, 422 sunitinib) | primarymedian follow-up 25.2 monthsMotzer 2018 | median 11.6 months (8.7–15.5) | median 8.4 months (7.0–10.8) | HR 0.82P=0.03Hazard ratio for disease progression or death with a 99.1% confidence interval of 0.64 to 1.05; the difference did not meet the prespecified threshold of P=0.009 for statistical significance. |
| OS | primaryMotzer 2018 | 78% at 18 mo (74–81%) | median 32.9 months; 68% at 18 mo (63–72%) | HR 0.68P<0.001Secondary end point. Hazard ratio for death with a 99.8% confidence interval of 0.49 to 0.95. Median overall survival was not reached with nivolumab plus ipilimumab. |
| OSIntermediate- and poor-risk patients | long term-updatemedian follow-up 99.1 monthsTannir 2024 | — | — | HR 0.69 (95% CI 0.59–0.81)Primary population of the 8-year report. Hazard ratio in the intention-to-treat population 0.72 (0.62 to 0.83) and, exploratory, in favourable-risk patients 0.82 (0.60 to 1.13). |
| PFSIntermediate- and poor-risk patients | long term-updatemedian follow-up 99.1 monthsTannir 2024 | 25.4% at 90 mo | 8.5% at 90 mo | Independent radiology review committee assessment. Landmark probabilities, not medians. |
| ORRFavourable-risk patients (exploratory) | exploratorymedian follow-up 99.1 monthsTannir 2024 | 29.6% | 51.6% | Exploratory analysis in favourable-risk patients; the co-primary end points were not tested in this group. |
| OSIntermediate- and poor-risk patients | finalmedian follow-up 9.3 yearsChoueiri 2026 | 30.2% at 9 y | 18.7% at 9 y | HR 0.69 (95% CI 0.59–0.81)Final analysis. The 108-month values are survival probabilities, not medians. |
| OS | finalmedian follow-up 9.3 yearsChoueiri 2026 | 31.4% at 9 y | 19.5% at 9 y | HR 0.71 (95% CI 0.62–0.82)Final analysis, secondary population. |
| OSFavourable-risk patients (exploratory) | exploratorymedian follow-up 9.3 yearsChoueiri 2026 | 35.3% at 9 y | 21.8% at 9 y | HR 0.80 (95% CI 0.59–1.09)Exploratory subgroup of the final analysis; the interval includes 1. |
| Endpoint | Analysis | Nivolumab plus ipilimumab | Sunitinib | Effect |
|---|---|---|---|---|
| OSIntermediate- and poor-risk patients (425 nivolumab plus ipilimumab, 422 sunitinib) | primarymedian follow-up 25.2 monthsMotzer 2018 | 75% at 18 mo (70–78%) | median 26 months; 60% at 18 mo (55–65%) | HR 0.63P<0.001Hazard ratio for death with a 99.8% confidence interval of 0.44 to 0.89 (full text); the interval is not a 95% interval. Median overall survival was not reached with nivolumab plus ipilimumab. |
| ORRIntermediate- and poor-risk patients (425 nivolumab plus ipilimumab, 422 sunitinib) | primarymedian follow-up 25.2 monthsMotzer 2018 | 42% (37–47%) | 27% (22–31%) | P<0.001Complete responses occurred in 40 patients (9%) with nivolumab plus ipilimumab and 5 patients (1%) with sunitinib. |
| PFSIntermediate- and poor-risk patients (425 nivolumab plus ipilimumab, 422 sunitinib) | primarymedian follow-up 25.2 monthsMotzer 2018 | median 11.6 months (8.7–15.5) | median 8.4 months (7.0–10.8) | HR 0.82P=0.03Hazard ratio for disease progression or death with a 99.1% confidence interval of 0.64 to 1.05; the difference did not meet the prespecified threshold of P=0.009 for statistical significance. |
| OS | primaryMotzer 2018 | 78% at 18 mo (74–81%) | median 32.9 months; 68% at 18 mo (63–72%) | HR 0.68P<0.001Secondary end point. Hazard ratio for death with a 99.8% confidence interval of 0.49 to 0.95. Median overall survival was not reached with nivolumab plus ipilimumab. |
| OSIntermediate- and poor-risk patients | long term-updatemedian follow-up 99.1 monthsTannir 2024 | — | — | HR 0.69 (95% CI 0.59–0.81)Primary population of the 8-year report. Hazard ratio in the intention-to-treat population 0.72 (0.62 to 0.83) and, exploratory, in favourable-risk patients 0.82 (0.60 to 1.13). |
| PFSIntermediate- and poor-risk patients | long term-updatemedian follow-up 99.1 monthsTannir 2024 | 25.4% at 90 mo | 8.5% at 90 mo | Independent radiology review committee assessment. Landmark probabilities, not medians. |
| ORRFavourable-risk patients (exploratory) | exploratorymedian follow-up 99.1 monthsTannir 2024 | 29.6% | 51.6% | Exploratory analysis in favourable-risk patients; the co-primary end points were not tested in this group. |
| OSIntermediate- and poor-risk patients | finalmedian follow-up 9.3 yearsChoueiri 2026 | 30.2% at 9 y | 18.7% at 9 y | HR 0.69 (95% CI 0.59–0.81)Final analysis. The 108-month values are survival probabilities, not medians. |
| OS | finalmedian follow-up 9.3 yearsChoueiri 2026 | 31.4% at 9 y | 19.5% at 9 y | HR 0.71 (95% CI 0.62–0.82)Final analysis, secondary population. |
| OSFavourable-risk patients (exploratory) | exploratorymedian follow-up 9.3 yearsChoueiri 2026 | 35.3% at 9 y | 21.8% at 9 y | HR 0.80 (95% CI 0.59–1.09)Exploratory subgroup of the final analysis; the interval includes 1. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.69 | 0.59–0.81 |
| OS | 0.69 | 0.59–0.81 |
| OS | 0.71 | 0.62–0.82 |
| OS | 0.8 | 0.59–1.09 |
- Sunitinib (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Sunitinib |
|---|---|
| 0 | 100.0% |
| 16 | 65.3% |
| 33 | 41.5% |
| 49 | 27.1% |
| 65 | 17.7% |
- Nivolumab plus ipilimumab (experimental)
- Sunitinib (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 | Sunitinib |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 7 | 65.8% | 56.1% |
| 15 | 40.8% | 29.0% |
| 22 | 26.9% | 16.3% |
| 29 | 17.7% | 9.1% |
Appears in
Sources
Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018;378(14):1277-1290.
Tannir NM, Albigès L, McDermott DF, Burotto M, Choueiri TK, Hammers HJ, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 8-year follow-up results of efficacy and safety from the phase III CheckMate 214 trial. Ann Oncol. 2024;35(11):1026-1038.
Choueiri TK, Albigès L, McDermott DF, Hammers HJ, Escudier B, Burotto M, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: final analysis of efficacy and safety from the phase III CheckMate 214 trial. Ann Oncol. 2026;37(7):960-973.