KEYNOTE-016
Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors
Phase 2N = 41NCT01876511
- Population
- Patients with progressive metastatic carcinoma, with or without mismatch-repair deficiency
- Design
- Phase 2 study of pembrolizumab 10 mg per kilogram of body weight every 14 days in three non-randomised cohorts: mismatch repair-deficient colorectal cancer, mismatch repair-proficient colorectal cancer and mismatch repair-deficient cancers that were not colorectal. Co-primary endpoints were the immune-related objective response rate and the 20-week immune-related progression-free survival rate.
- Primary endpoint
- ORR, PFS
- Arms
- dMMR colorectal cancer (experimental): Pembrolizumab 10 mg/kg every 14 days
- pMMR colorectal cancer (experimental): Pembrolizumab 10 mg/kg every 14 days
- dMMR non-colorectal cancers (experimental): Pembrolizumab 10 mg/kg every 14 days
- People
- Le DT
PFSHR 0.1OSHR 0.22
Show the numbers
| Endpoint | Analysis | dMMR colorectal cancer / pMMR colorectal cancer / dMMR non-colorectal cancers | Control | Effect |
|---|---|---|---|---|
| ORREvaluated patients in each cohort (4 of 10, 0 of 18 and 5 of 7)Immune-related objective response rate (co-primary endpoint) | primaryLe 2015 | 40% | — | Cohorts, not randomised arms. Response counts: 4 of 10, 0 of 18 and 5 of 7 patients. |
| PFSEvaluated patients in each cohort (7 of 9, 2 of 18 and 4 of 6)20-week immune-related progression-free survival rate (co-primary endpoint) | primaryLe 2015 | 78% | — | Cohorts, not randomised arms. Counts: 7 of 9, 2 of 18 and 4 of 6 patients. |
| PFSdMMR versus pMMR colorectal cancer cohorts | primaryLe 2015 | median 2.2 months | — | HR 0.1P<0.001Median progression-free survival was not reached in the dMMR colorectal cohort. Hazard ratio for progression or death, dMMR versus pMMR colorectal cohort; a comparison between non-randomised cohorts. |
| OSdMMR versus pMMR colorectal cancer cohorts | primaryLe 2015 | median 5 months | — | HR 0.22P=0.05Median overall survival was not reached in the dMMR colorectal cohort. Hazard ratio for death, dMMR versus pMMR colorectal cohort; a comparison between non-randomised cohorts. |
| Endpoint | Analysis | dMMR colorectal cancer / pMMR colorectal cancer / dMMR non-colorectal cancers | Control | Effect |
|---|---|---|---|---|
| ORREvaluated patients in each cohort (4 of 10, 0 of 18 and 5 of 7)Immune-related objective response rate (co-primary endpoint) | primaryLe 2015 | 40% | — | Cohorts, not randomised arms. Response counts: 4 of 10, 0 of 18 and 5 of 7 patients. |
| PFSEvaluated patients in each cohort (7 of 9, 2 of 18 and 4 of 6)20-week immune-related progression-free survival rate (co-primary endpoint) | primaryLe 2015 | 78% | — | Cohorts, not randomised arms. Counts: 7 of 9, 2 of 18 and 4 of 6 patients. |
| PFSdMMR versus pMMR colorectal cancer cohorts | primaryLe 2015 | median 2.2 months | — | HR 0.1P<0.001Median progression-free survival was not reached in the dMMR colorectal cohort. Hazard ratio for progression or death, dMMR versus pMMR colorectal cohort; a comparison between non-randomised cohorts. |
| OSdMMR versus pMMR colorectal cancer cohorts | primaryLe 2015 | median 5 months | — | HR 0.22P=0.05Median overall survival was not reached in the dMMR colorectal cohort. Hazard ratio for death, dMMR versus pMMR colorectal cohort; a comparison between non-randomised cohorts. |
- pMMR colorectal cancer (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | pMMR colorectal cancer |
|---|---|
| 0 | 100.0% |
| 1 | 73.0% |
| 3 | 38.9% |
| 4 | 28.4% |
| 6 | 15.1% |
- pMMR colorectal cancer (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | pMMR colorectal cancer |
|---|---|
| 0 | 100.0% |
| 3 | 66.0% |
| 6 | 43.5% |
| 9 | 28.7% |
| 13 | 16.5% |