KEYNOTE-146
Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: endometrial carcinoma cohort of the phase 1b/2 Study 111/KEYNOTE-146
Phase 1/2N = 108NCT02501096
- Population
- Previously treated advanced endometrial carcinoma regardless of microsatellite instability status (11 MSI-high, 94 microsatellite-stable tumours in the subgroup analysis)
- Design
- Phase 1b/2 study of selected solid tumours (Study 111/KEYNOTE-146); this record covers the endometrial carcinoma cohort. Lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks, in 3-week cycles. Tumour assessments by investigators according to immune-related RECIST. ClinicalTrials.gov lists 357 participants across all tumour cohorts; the endometrial cohort reported in the paper is 108 patients.
- Primary endpoint
- ORR
- Arms
- Lenvatinib plus pembrolizumab (single arm) (experimental, n = 108): Lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks
- People
- Makker V, Study 111/KEYNOTE-146
Show the numbers
| Endpoint | Analysis | Lenvatinib plus pembrolizumab (single arm) | Control | Effect |
|---|---|---|---|---|
| ORR108 previously treated patients with endometrial carcinomaObjective response rate at week 24 (primary endpoint), investigator assessment by immune-related RECIST | primarymedian follow-up 18.7 monthsMakker 2020 | 38% (28.8–47.8%) | — | Single-arm cohort; not comparable with randomised arms. |
| ORRMSI-high subgroup (n = 11)Objective response rate at week 24, investigator assessment by immune-related RECIST | primaryMakker 2020 | 63.6% (30.8–89.1%) | — | Very small subgroup. |
| ORRMicrosatellite-stable subgroup (n = 94)Objective response rate at week 24, investigator assessment by immune-related RECIST | primaryMakker 2020 | 36.2% (26.5–46.7%) | — | — |
| PFS108 previously treated patients with endometrial carcinoma | primarymedian follow-up 18.7 monthsMakker 2020 | median 7.4 months (5.3–8.7) | — | Secondary endpoint; regardless of tumour MSI status. |
| OS108 previously treated patients with endometrial carcinoma | primarymedian follow-up 18.7 monthsMakker 2020 | median 16.7 months | — | Secondary endpoint. The abstract gives the 95% CI as 15.0 months to not estimable; the upper bound is not encoded here. |
| Endpoint | Analysis | Lenvatinib plus pembrolizumab (single arm) | Control | Effect |
|---|---|---|---|---|
| ORR108 previously treated patients with endometrial carcinomaObjective response rate at week 24 (primary endpoint), investigator assessment by immune-related RECIST | primarymedian follow-up 18.7 monthsMakker 2020 | 38% (28.8–47.8%) | — | Single-arm cohort; not comparable with randomised arms. |
| ORRMSI-high subgroup (n = 11)Objective response rate at week 24, investigator assessment by immune-related RECIST | primaryMakker 2020 | 63.6% (30.8–89.1%) | — | Very small subgroup. |
| ORRMicrosatellite-stable subgroup (n = 94)Objective response rate at week 24, investigator assessment by immune-related RECIST | primaryMakker 2020 | 36.2% (26.5–46.7%) | — | — |
| PFS108 previously treated patients with endometrial carcinoma | primarymedian follow-up 18.7 monthsMakker 2020 | median 7.4 months (5.3–8.7) | — | Secondary endpoint; regardless of tumour MSI status. |
| OS108 previously treated patients with endometrial carcinoma | primarymedian follow-up 18.7 monthsMakker 2020 | median 16.7 months | — | Secondary endpoint. The abstract gives the 95% CI as 15.0 months to not estimable; the upper bound is not encoded here. |
- Lenvatinib plus pembrolizumab (single arm) (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Lenvatinib plus pembrolizumab (single arm) |
|---|---|
| 0 | 100.0% |
| 5 | 62.6% |
| 9 | 43.0% |
| 14 | 26.9% |
| 19 | 16.9% |
- Lenvatinib plus pembrolizumab (single arm) (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Lenvatinib plus pembrolizumab (single arm) |
|---|---|
| 0 | 100.0% |
| 10 | 66.0% |
| 21 | 41.8% |
| 31 | 27.6% |
| 42 | 17.5% |