Efficacy and Safety Study of First-line Treatment With Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Women With Persistent, Recurrent, or Metastatic Cervical Cancer (MK-3475-826/KEYNOTE-826)
Summary
The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) plus one of four platinum-based chemotherapy regimens compared to the efficacy and safety of placebo plus one of four platinum-based chemotherapy regimens in the treatment of adult women with persistent, recurrent, or metastatic cervical cancer. Possible chemotherapy regimens include: paclitaxel plus cisplatin with or without bevacizumab and paclitaxel plus carboplatin with or without bevacizumab. The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy with respect to: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by the Investigator, or, 2) Overall Survival (OS).
Timeline
- Start
- 2018-10-25
- Primary completion
- 2022-10-03
- Completion
- 2024-06-04
Outcome
Met primary endpoint
paper CONCLUSIONS: Progression-free and overall survival were significantly longer with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic cervical cancer PMID 34534429 ↗
paper In 548 patients with a PD-L1 combined positive score of 1 or more, median progression-free survival was 10.4 months in the pembrolizumab group and 8.2 months in the placebo group PMID 34534429 ↗
paper Overall survival at 24 months was 53.0% in the pembrolizumab group and 41.7% in the placebo group PMID 34534429 ↗
Publications
- Results Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yanez E, Gumus M, Olivera Hurtado de Mendoza M, Samouelian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. doi: 10.1200/JCO.23.00914. Epub 2023 Nov 1.
- Kim YM, Nishio S, Kim SI, Hasegawa K, Dubot C, Caceres MV, Tewari KS, Lorusso D, Lee JW, Liou WS, Li K, Tekin C, Colombo N, Monk BJ. Pembrolizumab plus chemotherapy with or without bevacizumab in East Asian participants with persistent, recurrent, or metastatic cervical cancer: results from KEYNOTE-826 final analysis. J Gynecol Oncol. 2025 Jul;36(4):e110. doi: 10.3802/jgo.2025.36.e110.
- Monk BJ, van Mens S, Hale O, Boer J, van Hees F, Swami S, Muston D, Tekin C, Keefe S, Monberg M. Cost-Effectiveness of Pembrolizumab as First-Line Treatment in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer in the United States. Oncol Ther. 2025 Mar;13(1):85-98. doi: 10.1007/s40487-024-00311-5. Epub 2024 Nov 5.
- Lorusso D, Colombo N, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yanez E, Gumus M, Olivera M, Samouelian V, Castonguay V, Arkhipov A, Li K, Toker S, Tekin C, Tewari KS, Monk BJ. Pembrolizumab plus chemotherapy for advanced and recurrent cervical cancer: final analysis according to bevacizumab use in the randomized KEYNOTE-826 study. Ann Oncol. 2025 Jan;36(1):65-75. doi: 10.1016/j.annonc.2024.10.002. Epub 2024 Oct 10.
- Tewari KS, Colombo N, Monk BJ, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yanez E, Gumus M, Olivera Hurtado de Mendoza M, Samouelian V, Castonguay V, Arkhipov A, Tekin C, Li K, Toker S, Keefe SM, Lorusso D. Pembrolizumab or Placebo Plus Chemotherapy With or Without Bevacizumab for Persistent, Recurrent, or Metastatic Cervical Cancer: Subgroup Analyses From the KEYNOTE-826 Randomized Clinical Trial. JAMA Oncol. 2024 Feb 1;10(2):185-192. doi: 10.1001/jamaoncol.2023.5410.
- Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yanez E, Gumus M, Hurtado de Mendoza MO, Samouelian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. doi: 10.1016/S1470-2045(23)00052-9. Epub 2023 Mar 3.
- Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yanez E, Gumus M, Olivera Hurtado de Mendoza M, Samouelian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. doi: 10.1056/NEJMoa2112435. Epub 2021 Sep 18.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Pembrolizumab | Monoclonal antibody | 200 mg | Intravenous |
| Background | Bevacizumab | Monoclonal antibody | 15 mg/kg | Intravenous |
| Background | Carboplatin | Small molecule | — | Intravenous |
| Background | Cisplatin | Other / unclassified | 50 mg/m2 | Intravenous |
| Background | Paclitaxel | Small molecule | 175 mg/m2 | Intravenous |