ENGOT-cx11/KEYNOTE-A18: A phase III, randomized, double-blind study of pembrolizumab with chemoradiotherapy in patients with high-risk locally advanced cervical cancer.

Author:

Lorusso Domenica1,Colombo Nicoletta2,Coleman Robert L.3,Randall Leslie M.4,Duska Linda R.5,Xiang Yang6,Hasegawa Kosei7,Rodrigues Angelica Nogueira8,Cibula David9,Mirza Mansoor Raza10,You Benoit11,Oaknin Ana12,Christiaens Melissa13,Taskiran Cagatay14,Braicu Elena Ioana15,Korach Jacob16,Marth Christian17,Keefe Stephen Michael18,Puglisi Martina19,Pignata Sandro20

Affiliation:

1. Fondazione IRCCS, Foundation Policlinico Universitario Agostino Gemelli IRCCS, Istituto Nazionale dei Tumori, Milan, Italy;

2. MANGO and Europen Institute of Oncology, Milan, Italy;

3. The University of Texas MD Anderson Cancer Center, Houston, TX;

4. Massey Cancer Center, Virginia Commonwealth University, Richmond, VA;

5. University of Virginia, Charlottesville, VA;

6. Peking Union Medical College Hospital, Beijing, China;

7. Saitama Medical University International Medical Center, Hidaka, Japan;

8. Federal University of Minas Gerais Brazil and Brazilian Group of Gynecologic Oncology, Belo Horizonte, Brazil;

9. Grand Hôpital de Charleroi, Prague, Czech Republic;

10. Nordic Society of Gynaecological Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;

11. Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, EMR UCBL/HCL 3738, Lyon, GINECO & GINEGEPS, Lyon, France;

12. Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain;

13. UZ Leuven, Leuven, Belgium;

14. TRSGO and Koc University School of Medicine, Istanbul, Turkey;

15. Department of Gynecology, Charité Medical University, Berlin, Germany;

16. Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel;

17. Department of Gynecology and Obstetrics, Medical University of Innsbruck, Innsbruck, Austria;

18. Merck & Co., Inc., Kenilworth, NJ;

19. MSD United Kingdom, UK, United Kingdom;

20. Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy;

Abstract

TPS6096 Background: High-risk locally advanced cervical cancer has a poor prognosis, and more than half of patients recur in 2 y. 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 (pembro) may be enhanced by concurrent chemoradiotherapy (CRT). After the KEYNOTE-158 study, in which pembro showed durable antitumor activity, pembro monotherapy was approved for patients with PD-L1–positive recurrent or metastatic cervical cancer who progressed during or after chemotherapy. ENGOT-cx11/KEYNOTE-A18 (NCT04221945) is a phase III, randomized, placebo-controlled study evaluating pembro with concurrent CRT for the treatment of locally advanced cervical cancer. Methods: Approximately 980 patients with high-risk (FIGO 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 pembro 200 mg every 3 wk (Q3W) + CRT followed by 15 cycles of pembro 400 mg Q6W or 5 cycles of placebo Q3W + CRT followed by 15 cycles of placebo Q6W. The CRT regimen includes 5 cycles (with 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 pembro (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs placebo (~2 y) 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 are PFS at 2 y, OS at 3 y, complete response at 12 wk, ORR, PFS and OS in PD-L1–positive patients, EORTC QLQ-C30 and QLQ-CX24, and safety. Enrollment is ongoing. Clinical trial information: NCT04221945.

Funder

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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