CheckMate 069
Study of Nivolumab (BMS-936558) Plus Ipilimumab Compared With Ipilimumab Alone in the Treatment of Previously Untreated, Unresectable, or Metastatic Melanoma
Phase 2N = 142NCT01927419
- Population
- Previously untreated metastatic melanoma (BRAF V600 wild-type population for the primary end point)
- Design
- Double-blind randomised (2:1) phase 2 trial in untreated metastatic melanoma: ipilimumab 3 mg per kilogram with either nivolumab 1 mg per kilogram or placebo every 3 weeks for four doses, then nivolumab 3 mg per kilogram or placebo every 2 weeks until progression or unacceptable toxic effects. The primary end point was the investigator-assessed confirmed objective response rate in patients with BRAF V600 wild-type tumours. In the full text, 142 patients were randomised (95 to the combination, 47 to ipilimumab alone): 109 with BRAF wild-type and 33 with BRAF V600 mutation-positive tumours.
- Primary endpoint
- ORR
- Arms
- Nivolumab plus ipilimumab (experimental, n = 95): 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
- Ipilimumab plus placebo (control, n = 47): Ipilimumab 3 mg per kilogram every 3 weeks for four doses plus placebo, then placebo every 2 weeks
- People
- Postow MA, senior author Hodi FS
Δ ORR+50 pointsPFSHR 0.40 (95% CI 0.23–0.68)
Show the numbers
| Endpoint | Analysis | Nivolumab plus ipilimumab | Ipilimumab plus placebo | Effect |
|---|---|---|---|---|
| ORRPatients with BRAF V600 wild-type tumours (72 and 37) | primaryPostow 2015 | 61% | 11% | P<0.001Confirmed objective response, investigator-assessed: 44 of 72 patients versus 4 of 37. Complete responses in 16 patients (22%) with the combination and none with ipilimumab alone. Median duration of response was not reached in either group. |
| PFSPatients with BRAF V600 wild-type tumours (72 and 37) | primaryPostow 2015 | — | median 4.4 months | HR 0.40 (95% CI 0.23–0.68)P<0.001Median progression-free survival was not reached with the combination. Hazard ratio for progression or death, combination versus ipilimumab. A key secondary end point (tested hierarchically after the primary response end point), not the primary end point. |
| Endpoint | Analysis | Nivolumab plus ipilimumab | Ipilimumab plus placebo | Effect |
|---|---|---|---|---|
| ORRPatients with BRAF V600 wild-type tumours (72 and 37) | primaryPostow 2015 | 61% | 11% | P<0.001Confirmed objective response, investigator-assessed: 44 of 72 patients versus 4 of 37. Complete responses in 16 patients (22%) with the combination and none with ipilimumab alone. Median duration of response was not reached in either group. |
| PFSPatients with BRAF V600 wild-type tumours (72 and 37) | primaryPostow 2015 | — | median 4.4 months | HR 0.40 (95% CI 0.23–0.68)P<0.001Median progression-free survival was not reached with the combination. Hazard ratio for progression or death, combination versus ipilimumab. A key secondary end point (tested hierarchically after the primary response end point), not the primary end point. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.4 | 0.23–0.68 |
- Ipilimumab plus placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Ipilimumab plus placebo |
|---|---|
| 0 | 100.0% |
| 3 | 62.3% |
| 6 | 38.9% |
| 8 | 28.4% |
| 11 | 17.7% |