Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11/GOG-3047)
Summary
The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer. The primary hypotheses are that pembrolizumab plus concurrent chemoradiotherapy is superior to placebo plus concurrent chemoradiotherapy with respect to progression-free survival and overall survival. Once the study objectives have been met or the study has ended, participants will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.
Timeline
- Start
- 2020-05-12
- Primary completion
- 2025-01-07
- Completion
- 2026-01-26
Outcome
Met primary endpoint
registry analysis (superiority test); Chemoradiotherapy + Pembrolizumab vs Chemoradiotherapy + Placebo for Pembrolizumab; p = 0.0004; Hazard Ratio (HR) 0.72 (95% CI 0.59 to 0.87) NCT04221945 ↗
registry analysis (superiority test); Chemoradiotherapy + Pembrolizumab vs Chemoradiotherapy + Placebo for Pembrolizumab; p = 0.0076; Hazard Ratio (HR) 0.73 (95% CI 0.57 to 0.94) NCT04221945 ↗
Publications
- Results Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejia F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampe R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024 Apr 6;403(10434):1341-1350. doi: 10.1016/S0140-6736(24)00317-9. Epub 2024 Mar 20.
- Results Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Cvek J, Randall L, Pereira de Santana Gomes AJ, Contreras Mejia F, Helpman L, Akilli H, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Colombo N, Chang CL, Bednarikova M, Zhu H, Oaknin A, Christiaens M, Petru E, Usami T, Liu P, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Oct 5;404(10460):1321-1332. doi: 10.1016/S0140-6736(24)01808-7. Epub 2024 Sep 14.
- Randall L, Xiang Y, Matsumoto T, Giannarelli D, Milla DP, Lopez KA, Acevedo A, Vizkeleti J, Salani R, Nogueira-Rodrigues A, Mejia FC, Korach J, Akilli H, Lee JY, Saevets VV, Samouelian V, Sehouli J, Tharavichikul E, Sukhin V, Colombo N, Chang CL, Cueva JF, Lalondrelle S, Petru E, Szamreta E, Nguyen AM, Yamada K, Li K, Pignata S, Lorusso D. Patient-reported outcomes from the phase 3, randomized, double-blind, placebo-controlled ENGOT-cx11/GOG-3047/KEYNOTE-A18 study of pembrolizumab plus concurrent chemoradiotherapy in participants with high-risk locally advanced cervical cancer. Gynecol Oncol. 2025 Aug;199:88-95. doi: 10.1016/j.ygyno.2025.06.003. Epub 2025 Jun 30.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Pembrolizumab | Monoclonal antibody | 400 mg | Intravenous |
| Background | Cisplatin | Other / unclassified | 40 mg/m2 | Intravenous |