KEYNOTE-B21
Pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in newly diagnosed, high-risk endometrial cancer (ENGOT-en11/GOG-3053/KEYNOTE-B21)
Phase 3N = 1,095NCT04634877
- Population
- Newly diagnosed high-risk endometrial cancer after surgery with curative intent: FIGO stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology; dMMR n=281, pMMR n=814
- Design
- Randomised, double-blind, phase 3 trial. After curative-intent surgery with no evidence of disease and no prior radiotherapy or systemic therapy, patients received pembrolizumab 200 mg or placebo every 3 weeks for six cycles with carboplatin-paclitaxel, then pembrolizumab 400 mg or placebo every 6 weeks for six cycles; radiotherapy was at investigator discretion. Primary endpoints investigator-assessed disease-free survival and overall survival in the intention-to-treat population. 1095 patients were randomised (545 pembrolizumab, 550 placebo); interim analysis data cut-off 4 March 2024. ClinicalTrials.gov lists an estimated enrolment of 990.
- Primary endpoint
- DFS, OS
- Arms
- Placebo plus chemotherapy (control, n = 550): Placebo every 3 weeks for six cycles with carboplatin-paclitaxel, then placebo every 6 weeks for six cycles
- Pembrolizumab plus chemotherapy (experimental, n = 545): Pembrolizumab 200 mg every 3 weeks for six cycles with carboplatin-paclitaxel, then pembrolizumab 400 mg every 6 weeks for six cycles
- People
- Van Gorp T
DFSHR 1.02 (95% CI 0.79–1.32)Δ 24-month DFS−1 pointsDFSHR 0.31 (95% CI 0.14–0.69)DFSHR 1.20 (95% CI 0.91–1.57)DFSHR 0.31 (95% CI 0.14–0.69)Δ 24-month DFS+12.2 points
Show the numbers
| Endpoint | Analysis | Pembrolizumab plus chemotherapy | Placebo plus chemotherapy | Effect |
|---|---|---|---|---|
| DFSInvestigator-assessed disease-free survival (primary endpoint); interim analysis, data cut-off 4 March 2024 | interimVan 2024 | 75% at 2 y | 76% at 2 y | HR 1.02 (95% CI 0.79–1.32)P=0.570119 (22%) DFS events in the pembrolizumab group and 121 (22%) in the placebo group. 1095 patients were randomised (545 pembrolizumab, 550 placebo). |
| DFSdMMR subgroup of the ITT population (n=281; preplanned subgroup by stratification factor, no formal hypothesis testing)Investigator-assessed disease-free survival in the dMMR population; interim analysis (Annals of Oncology report) | exploratoryVan 2024 | — | — | HR 0.31 (95% CI 0.14–0.69)The abstract describes this as a preplanned subgroup analysis for a stratification factor. |
| DFSpMMR subgroup of the ITT population (n=814; preplanned subgroup by stratification factor)Investigator-assessed disease-free survival in the pMMR population; interim analysis | exploratoryVan 2024 | — | — | HR 1.20 (95% CI 0.91–1.57) |
| DFSdMMR subgroup of the ITT population (141 pembrolizumab, 140 placebo); protocol-prespecified subgroup, no formal hypothesis testingInvestigator-assessed disease-free survival in dMMR tumours: 2-year DFS rate; median DFS not reached in either group | exploratorySlomovitz 2025 | 92.4% at 2 y (84.4–96.4%) | 80.2% at 2 y (70.8–86.9%) | HR 0.31 (95% CI 0.14–0.69)Interim analysis; the abstract states that longer-term follow-up will be evaluated at the final analysis. |
| Grade 3 or worse adverse eventsPatients assessed for safety (543 pembrolizumab, 549 placebo)Grade 3 or worse adverse events | interimVan 2024 | 71% | 63% | 386 of 543 patients with pembrolizumab versus 348 of 549 with placebo; no treatment-related grade 5 adverse events. |
| Endpoint | Analysis | Pembrolizumab plus chemotherapy | Placebo plus chemotherapy | Effect |
|---|---|---|---|---|
| DFSInvestigator-assessed disease-free survival (primary endpoint); interim analysis, data cut-off 4 March 2024 | interimVan 2024 | 75% at 2 y | 76% at 2 y | HR 1.02 (95% CI 0.79–1.32)P=0.570119 (22%) DFS events in the pembrolizumab group and 121 (22%) in the placebo group. 1095 patients were randomised (545 pembrolizumab, 550 placebo). |
| DFSdMMR subgroup of the ITT population (n=281; preplanned subgroup by stratification factor, no formal hypothesis testing)Investigator-assessed disease-free survival in the dMMR population; interim analysis (Annals of Oncology report) | exploratoryVan 2024 | — | — | HR 0.31 (95% CI 0.14–0.69)The abstract describes this as a preplanned subgroup analysis for a stratification factor. |
| DFSpMMR subgroup of the ITT population (n=814; preplanned subgroup by stratification factor)Investigator-assessed disease-free survival in the pMMR population; interim analysis | exploratoryVan 2024 | — | — | HR 1.20 (95% CI 0.91–1.57) |
| DFSdMMR subgroup of the ITT population (141 pembrolizumab, 140 placebo); protocol-prespecified subgroup, no formal hypothesis testingInvestigator-assessed disease-free survival in dMMR tumours: 2-year DFS rate; median DFS not reached in either group | exploratorySlomovitz 2025 | 92.4% at 2 y (84.4–96.4%) | 80.2% at 2 y (70.8–86.9%) | HR 0.31 (95% CI 0.14–0.69)Interim analysis; the abstract states that longer-term follow-up will be evaluated at the final analysis. |
| Grade 3 or worse adverse eventsPatients assessed for safety (543 pembrolizumab, 549 placebo)Grade 3 or worse adverse events | interimVan 2024 | 71% | 63% | 386 of 543 patients with pembrolizumab versus 348 of 549 with placebo; no treatment-related grade 5 adverse events. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 1.02 | 0.79–1.32 |
| DFS | 0.31 | 0.14–0.69 |
| DFS | 1.2 | 0.91–1.57 |
| DFS | 0.31 | 0.14–0.69 |
Appears in
Sources
Van Gorp T, Cibula D, Lv W, Backes F, Ortaç F, Hasegawa K, et al. ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer. Ann Oncol. 2024;35(11):968-980.
Slomovitz BM, Cibula D, Lv W, Ortaç F, Hietanen S, Backes F, et al. Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors. J Clin Oncol. 2025;43(3):251-259.