CheckMate 142
A Phase 2 Clinical Trial of Nivolumab, or Nivolumab Combinations in Recurrent and Metastatic Microsatellite Instability High (MSI-H) and Non-MSI-H Colon Cancer
Phase 2NCT02060188
- Population
- Recurrent or metastatic dMMR/MSI-H colorectal cancer: previously treated (progression on, or intolerance of, at least one prior line including a fluoropyrimidine and oxaliplatin or irinotecan) and previously untreated in the metastatic setting
- Design
- Multicohort, open-label, non-randomised phase 2 trial. Cohorts recorded here: previously treated patients given nivolumab 3 mg/kg every 2 weeks (31 sites in eight countries); previously treated patients given nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses, then nivolumab 3 mg/kg every 2 weeks; and first-line patients given nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks. The primary endpoint in each cohort was investigator-assessed objective response rate (RECIST 1.1).
- Primary endpoint
- ORR
- Arms
- Nivolumab (previously treated) (experimental, n = 74): Nivolumab 3 mg/kg every 2 weeks
- Nivolumab plus ipilimumab (previously treated) (experimental, n = 119): Nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses, then nivolumab 3 mg/kg every 2 weeks
- Nivolumab plus low-dose ipilimumab (first line) (experimental, n = 45): Nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks
- People
- Overman MJ
Show the numbers
| Endpoint | Analysis | Nivolumab (previously treated) / Nivolumab plus ipilimumab (previously treated) / Nivolumab plus low-dose ipilimumab (first line) | Control | Effect |
|---|---|---|---|---|
| ORRAll treated patients (n=74)Investigator-assessed objective response rate (primary endpoint) | primarymedian follow-up 12 monthsOverman 2017 | 31.1% (20.8–42.9%) | — | Disease control for 12 weeks or longer in 69% (95% CI 57 to 79). Median duration of response not reached; eight responses lasted 12 months or longer. Median follow-up 12.0 months (IQR 8.6 to 18.0). |
| ORRPatients in the nivolumab plus ipilimumab cohort (n=119)Investigator-assessed objective response rate (primary endpoint) | primarymedian follow-up 13.4 monthsOverman 2018 | 55% (45.2–63.8%) | — | Disease control for 12 weeks or longer in 80%. Median duration of response not reached; 94% of responses were ongoing at data cutoff. Indirect comparison with the nivolumab cohort is not valid (separately enrolled cohorts). |
| PFSPatients in the nivolumab plus ipilimumab cohort (n=119)Progression-free survival rate at 9 and 12 months | primarymedian follow-up 13.4 monthsOverman 2018 | 76% at 9 mo; 71% at 12 mo | — | — |
| OSPatients in the nivolumab plus ipilimumab cohort (n=119)Overall survival rate at 9 and 12 months | primarymedian follow-up 13.4 monthsOverman 2018 | 87% at 9 mo; 85% at 12 mo | — | — |
| ORRTreated first-line patients (n=45)Investigator-assessed objective response rate (primary endpoint) | primarymedian follow-up 29 monthsLenz 2022 | 69% (53–82%) | — | Disease control rate 84% (95% CI 70.5 to 93.5); complete response rate 13%. Median duration of response not reached; 74% of responders had ongoing responses at cutoff. |
| PFSTreated first-line patients (n=45)Progression-free survival rate at 24 months | primarymedian follow-up 29 monthsLenz 2022 | 74% at 2 y | — | Median progression-free survival not reached; minimum follow-up 24.2 months. |
| OSTreated first-line patients (n=45)Overall survival rate at 24 months | primarymedian follow-up 29 monthsLenz 2022 | 79% at 2 y | — | Median overall survival not reached; minimum follow-up 24.2 months. |
| Endpoint | Analysis | Nivolumab (previously treated) / Nivolumab plus ipilimumab (previously treated) / Nivolumab plus low-dose ipilimumab (first line) | Control | Effect |
|---|---|---|---|---|
| ORRAll treated patients (n=74)Investigator-assessed objective response rate (primary endpoint) | primarymedian follow-up 12 monthsOverman 2017 | 31.1% (20.8–42.9%) | — | Disease control for 12 weeks or longer in 69% (95% CI 57 to 79). Median duration of response not reached; eight responses lasted 12 months or longer. Median follow-up 12.0 months (IQR 8.6 to 18.0). |
| ORRPatients in the nivolumab plus ipilimumab cohort (n=119)Investigator-assessed objective response rate (primary endpoint) | primarymedian follow-up 13.4 monthsOverman 2018 | 55% (45.2–63.8%) | — | Disease control for 12 weeks or longer in 80%. Median duration of response not reached; 94% of responses were ongoing at data cutoff. Indirect comparison with the nivolumab cohort is not valid (separately enrolled cohorts). |
| PFSPatients in the nivolumab plus ipilimumab cohort (n=119)Progression-free survival rate at 9 and 12 months | primarymedian follow-up 13.4 monthsOverman 2018 | 76% at 9 mo; 71% at 12 mo | — | — |
| OSPatients in the nivolumab plus ipilimumab cohort (n=119)Overall survival rate at 9 and 12 months | primarymedian follow-up 13.4 monthsOverman 2018 | 87% at 9 mo; 85% at 12 mo | — | — |
| ORRTreated first-line patients (n=45)Investigator-assessed objective response rate (primary endpoint) | primarymedian follow-up 29 monthsLenz 2022 | 69% (53–82%) | — | Disease control rate 84% (95% CI 70.5 to 93.5); complete response rate 13%. Median duration of response not reached; 74% of responders had ongoing responses at cutoff. |
| PFSTreated first-line patients (n=45)Progression-free survival rate at 24 months | primarymedian follow-up 29 monthsLenz 2022 | 74% at 2 y | — | Median progression-free survival not reached; minimum follow-up 24.2 months. |
| OSTreated first-line patients (n=45)Overall survival rate at 24 months | primarymedian follow-up 29 monthsLenz 2022 | 79% at 2 y | — | Median overall survival not reached; minimum follow-up 24.2 months. |
- Nivolumab plus ipilimumab (previously treated) (experimental)
Data table (modelled values)
| Months | Nivolumab plus ipilimumab (previously treated) |
|---|---|
| 0 | 100.0% |
| 3 | 91.7% |
| 6 | 83.3% |
| 10 | 74.1% |
| 13 | 71.0% |
- Nivolumab plus ipilimumab (previously treated) (experimental)
Data table (modelled values)
| Months | Nivolumab plus ipilimumab (previously treated) |
|---|---|
| 0 | 100.0% |
| 3 | 95.4% |
| 6 | 90.8% |
| 10 | 86.2% |
| 13 | 85.0% |
Appears in
Sources
Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182-1191.
Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, et al. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018;36(8):773-779.
Lenz HJ, Van Cutsem E, Luisa Limon M, Wong KYM, Hendlisz A, Aglietta M, et al. First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study. J Clin Oncol. 2022;40(2):161-170.