CheckMate 816
Neoadjuvant nivolumab plus platinum-based chemotherapy versus chemotherapy alone, followed by resection, in resectable non-small-cell lung cancer
Phase 3N = 358NCT02998528
- Population
- Resectable stage IB to IIIA non-small-cell lung cancer
- Design
- Open-label phase 3 trial. Three cycles of neoadjuvant nivolumab plus platinum-doublet chemotherapy or chemotherapy alone, followed by surgery. 505 patients were randomised in all; a third group (nivolumab plus ipilimumab) closed enrolment early and is not part of these comparisons. The efficacy comparison covers the 358 patients concurrently randomised to the two arms shown here.
- Primary endpoint
- EFS, pCR
- Arms
- Nivolumab plus chemotherapy (experimental, n = 179): Neoadjuvant nivolumab plus platinum-based chemotherapy, followed by surgery
- Chemotherapy alone (control, n = 179): Neoadjuvant platinum-based chemotherapy, followed by surgery
- People
- Forde PM, CheckMate 816 Investigators
EFSHR 0.63Δ median EFS+10.8 monthsΔ pCR+21.8 pointsOSHR 0.57OSHR 0.720 (95% CI 0.523–0.998)Δ 60-month OS+10.4 points
Show the numbers
| Endpoint | Analysis | Nivolumab plus chemotherapy | Chemotherapy alone | Effect |
|---|---|---|---|---|
| EFSConcurrently randomised patients (N = 358)Time to disease progression, disease recurrence or death, assessed by blinded independent review | primaryForde 2022 | median 31.6 months | median 20.8 months (14.0–26.7) | HR 0.63P=0.005Primary endpoint. The abstract reports the hazard ratio as 0.63 with a 97.38% CI of 0.43 to 0.91, so no ci95 is entered; the 95% CI for the nivolumab-plus-chemotherapy median is 30.2 to not reached. |
| pCRConcurrently randomised patients (N = 358)0% viable tumour in resected lung and lymph nodes, evaluated by blinded independent review | primaryForde 2022 | 24% (18–31%) | 2.2% (0.6–5.6%) | P<0.001Primary endpoint. Odds ratio 13.94 (99% CI 3.49 to 55.75). 83.2% vs 75.4% of randomised patients underwent surgery; grade 3 or 4 treatment-related adverse events 33.5% vs 36.9%. |
| OSConcurrently randomised patients (N = 358) | interimForde 2022 | — | — | HR 0.57Key secondary endpoint, first prespecified interim analysis. The 99.67% CI was 0.30 to 1.07 and the abstract states the result did not meet the criterion for significance. |
| OS358 patients concurrently randomised to nivolumab plus chemotherapy or chemotherapy alone | finalmedian follow-up 68.4 monthsForde 2025 | 65.4% at 5 y | 55% at 5 y | HR 0.720 (95% CI 0.523–0.998)P=0.048Planned analysis of overall survival, a key secondary endpoint. 179 patients per arm. |
| Endpoint | Analysis | Nivolumab plus chemotherapy | Chemotherapy alone | Effect |
|---|---|---|---|---|
| EFSConcurrently randomised patients (N = 358)Time to disease progression, disease recurrence or death, assessed by blinded independent review | primaryForde 2022 | median 31.6 months | median 20.8 months (14.0–26.7) | HR 0.63P=0.005Primary endpoint. The abstract reports the hazard ratio as 0.63 with a 97.38% CI of 0.43 to 0.91, so no ci95 is entered; the 95% CI for the nivolumab-plus-chemotherapy median is 30.2 to not reached. |
| pCRConcurrently randomised patients (N = 358)0% viable tumour in resected lung and lymph nodes, evaluated by blinded independent review | primaryForde 2022 | 24% (18–31%) | 2.2% (0.6–5.6%) | P<0.001Primary endpoint. Odds ratio 13.94 (99% CI 3.49 to 55.75). 83.2% vs 75.4% of randomised patients underwent surgery; grade 3 or 4 treatment-related adverse events 33.5% vs 36.9%. |
| OSConcurrently randomised patients (N = 358) | interimForde 2022 | — | — | HR 0.57Key secondary endpoint, first prespecified interim analysis. The 99.67% CI was 0.30 to 1.07 and the abstract states the result did not meet the criterion for significance. |
| OS358 patients concurrently randomised to nivolumab plus chemotherapy or chemotherapy alone | finalmedian follow-up 68.4 monthsForde 2025 | 65.4% at 5 y | 55% at 5 y | HR 0.720 (95% CI 0.523–0.998)P=0.048Planned analysis of overall survival, a key secondary endpoint. 179 patients per arm. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.72 | 0.523–0.998 |
- Nivolumab plus chemotherapy (experimental)
- Chemotherapy alone (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 chemotherapy | Chemotherapy alone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 20 | 64.5% | 51.4% |
| 40 | 41.6% | 26.4% |
| 59 | 27.4% | 14.0% |
| 79 | 17.7% | 7.2% |
Appears in
Sources
Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, et al. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022;386(21):1973-1985.
Forde PM, Spicer JD, Provencio M, Mitsudomi T, Awad MM, Wang C, et al. Overall Survival with Neoadjuvant Nivolumab plus Chemotherapy in Lung Cancer. N Engl J Med. 2025;393(8):741-752.