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261 ENGOT-cx11/GOG 3047/KEYNOTE-A18: phase 3 randomized study of pembrolizumab + chemoradiotherapy for high-risk locally advanced cervical cancer
  1. D Lorusso1,
  2. Y Xiang2,
  3. N Colombo3,
  4. RL Coleman4,
  5. LM Randall5,
  6. L Duska6,
  7. K Hasegawa7,
  8. A Nogueira-Rodrigues8,
  9. D Cibula9,
  10. MR Mirza10,
  11. B You11,
  12. A Oaknin12,
  13. M Christiaens13,
  14. C Taskiran14,
  15. J Sehouli15,
  16. J Korach16,
  17. C Marth17,
  18. K Yamada18,
  19. M Puglisi18 and
  20. S Pignata19
  1. 1Associate Professor of Obstetrics and Gynecology, Catholic University of Sacred Heart; Clinical Research Development Unit Fondazione Policlinico Gemelli IRCCS, Rome, Italy
  2. 2Department of Gynecology and Obstetrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
  3. 3Department of Gynecology, Instituto Europeo di Oncologia, Milan, Italy
  4. 4Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
  5. 5Department of Obstetrics and Gynecology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA
  6. 6Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, VA, USA
  7. 7Department of Gynecologic Oncology, Saitama Medical University, Hidaka, Saitama Prefecture, Japan
  8. 8Departamento de Clínica Médica, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
  9. 9Department of Obstetrics and Gynecology, General Faculty Hospital in Prague, First Faculty of Medicine, Charles University, Prague, Czech Republic
  10. 10Department of Oncology, Copenhagen University Hospital, Copenhagen, Denmark
  11. 11Department of Medical Oncology, CITOHL, IC-HCL, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France
  12. 12Department of Medical Oncology, Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
  13. 13Department of Radiation Oncology, Universitair Ziekenhuis Leuven, Leuven, Belgium
  14. 14Professor Koc University School of Medicine and VKV American Hospital, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology and Turkish Society of Gynecologic Oncology, Istanbul, Turkey
  15. 15Deparment of Gynecology, Charité–Universitätsmedizin Berlin, Berlin, Germany
  16. 16Gynecology Oncology Department, Sheba Medical Center, Ramat Gan, Israel
  17. 17Department of Obstetrics and Gynecology, Medizinische Universität Innsbruck, Innsbruck, Austria
  18. 18Clinical Development, Merck and Co., Inc., Kenilworth, NJ, USA
  19. 19Department of Uro-Gynaecological Oncology, Instituto Nazionale Tumori IRCCS Fondazione G Pascale, Italy

Abstract

Introduction/Background*High-risk locally advanced cervical cancer has a poor prognosis, and more than half of patients recur in 2 years. External beam radiotherapy (EBRT) with concurrent chemotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer. The immunostimulatory activity of the PD-1 inhibitor pembrolizumab may be enhanced by concurrent chemoradiotherapy (CCRT). After the KEYNOTE-158 study, in which pembrolizumab showed durable antitumor activity, pembrolizumab monotherapy was approved for patients with PD-L1–positive recurrent or metastatic cervical cancer who progressed during or after chemotherapy. ENGOT-cx11/GOG 3047/KEYNOTE-A18 (NCT04221945) is a phase 3, randomized, placebo-controlled study evaluating pembrolizumab with CCRT for the treatment of high-risk, locally advanced cervical cancer.

Methodology Approximately 980 patients with high-risk (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB with node-positive disease or stage III-IVA), locally advanced, histologically confirmed cervical cancer who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive either 5 cycles of pembrolizumab 200 mg every 3 weeks (Q3W) + CCRT followed by 15 cycles of pembrolizumab 400 mg Q6W or 5 cycles of placebo Q3W + CCRT followed by 15 cycles of placebo Q6W. CCRT includes 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT followed by brachytherapy. Randomization is stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cancer stage at screening (stage IB2-IIB vs III-IVA), and planned total radiotherapy dose. Treatment will continue until the patient has received 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 progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator and overall survival (OS). Secondary endpoints include PFS by blinded independent central review, PFS at 2 years, OS at 3 years, complete response at 12 weeks, objective response rate, PFS and OS by PD-L1 status, quality of life, and safety. Enrolment began May 2020 and is planned for 193 sites in 30 countries.

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