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164 ENGOT-cx11/GOG 3047/KEYNOTE-A18: a phase 3, randomized, double-blind study of pembrolizumab with chemoradiotherapy in patients with high-risk locally advanced cervical cancer
  1. D Lorusso1,
  2. N Colombo2,
  3. R Coleman3,
  4. L Randall4,
  5. L Duska5,
  6. Y Xiang6,
  7. K Hasegawa7,
  8. A Nogueira-Rodrigues8,
  9. D Cibula9,
  10. M Raza Mirza10,
  11. B You11,
  12. A Oaknin12,
  13. M Christiaens13,
  14. C Taskiran14,
  15. J Sehouli15,
  16. J Korach16,
  17. C Martin17,
  18. S Keefe18,
  19. M Puglisi18 and
  20. S Pignata19
  1. 1Università Cattolica del Sacro Cuore–Fondazione Policlinico Universitario, Italy
  2. 2Instituto Europeo di Oncologia, Italy
  3. 3University of Texas MD Anderson Cancer Center, USA
  4. 4Virginia Commonwealth University Health Massey Cancer Center, USA
  5. 5University of Virginia, USA
  6. 6Chinese Academy of Medical Sciences and Peking Union Medical College, China
  7. 7Saitama Medical University, Japan
  8. 8Universidade Federal de Minas Gerais, Brazil
  9. 9Department of Obstetrics and Gynecology, General Faculty Hospital in Prague, First Faculty of Medicine, Charles University, Czech Republic
  10. 10Copenhagen University Hospital, Denmark
  11. 11Institut de Cancerologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Université Claude Bernard Lyon 1, Univ Lyon, France
  12. 12Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Spain
  13. 13Universitair Ziekenhuis Leuven, Belgium
  14. 14American Hospital, Turkey
  15. 15Charité–Universitätsmedizin Berlin, Germany
  16. 16Sheba Medical Center, Israel
  17. 17Medizinische Universität Innsbruck, Austria
  18. 18Merck and Co., Inc., USA
  19. 19Istituto Nazionale Tumori IRCCS Fondazione G Pascale, Italy


Background High-risk locally advanced cervical cancer (CC) has a poor prognosis, and >50% of patients recur in 2 years. Concurrent chemoradiotherapy (CRT) may enhance the immunostimulatory activity of the PD-1 inhibitor pembrolizumab. After KEYNOTE-158, in which pembrolizumab demonstrated durable antitumor activity, pembrolizumab monotherapy was approved for patients with PD-L1–positive recurrent or metastatic CC who progressed during or after chemotherapy. ENGOT-cx11/KEYNOTE-A18 (NCT04221945) is a phase 3, randomized, placebo-controlled study evaluating pembrolizumab with concurrent CRT in locally advanced CC.

Trial design Approximately 980 patients with high-risk, locally advanced, histologically confirmed CC who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive 5 cycles of pembrolizumab 200 mg Q3W + CRT (5 cycles [with optional 6th cycle] of cisplatin 40 mg/m2 Q1W + external beam radiotherapy [EBRT] followed by brachytherapy) followed by 15 cycles of pembrolizumab 400 mg Q6W or 5 cycles of placebo Q3W + CRT followed by 15 cycles of placebo Q6W. Randomization is stratified by planned EBRT type, cancer stage at screening, and planned total radiotherapy dose. Treatment will continue until patient receives ≤20 cycles of pembrolizumab (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs placebo (~2 years) or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are PFS per RECIST v1.1 by blinded independent central review and OS. Secondary endpoints include PFS at 2 years, OS at 3 years, complete response at 12 weeks, ORR, PFS and OS in PD-L1–positive patients, and safety. Enrollment is ongoing.

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