Article Text

Download PDFPDF

393 Keynote-826: a phase 3, randomized, double-blind, placebo-controlled study of pembrolizumab plus chemotherapy for first-line treatment of persistent, recurrent, or metastatic cervical cancer
  1. K Tewari1,
  2. MV Caceres2,
  3. J Alexandre3,
  4. B Monk4,
  5. T Fehm5,
  6. N Colombo6,
  7. K Hasegawa7,
  8. C Dubot8,
  9. JJ Li9,
  10. K Stein10,
  11. S Keefe11 and
  12. R Shapira-Frommer12
  1. 1University of California, Irvine Medical Center, Orange, USA
  2. 2Instituto Ángel H Roffo, Department of Clinical Oncology, Buenos Aires, Argentina
  3. 3Hôpital Cochin, Cancer Oncology, Paris, France
  4. 4University of Arizona Cancer Center, Division of Gynecologic Oncology, Tucson, USA
  5. 5Heinrich-Heine-Universität Düsseldorf, Department of Gynecology and Obstetrics, Düsseldorf, Germany
  6. 6University of Milan-Bicocca, Division of Gynecologic Oncology, Milano, Italy
  7. 7Saitama Medical University International, Department of Obstetrics and Gynecology, Saitama, Japan
  8. 8Institut Curie, Department of Medical Oncology, Paris, France
  9. 9Merck and Co.- Inc., Statistics, Kenilworth, USA
  10. 10Merck and Co.- Inc., Oncology Clinical Development, Kenilworth, USA
  11. 11Merck and Co.- Inc., Late Stage Oncology Clinical Development, Kenilworth, USA
  12. 12Sheba Medical Center, The Ella Institute for Immuno-Oncology, Ramat Gan, Israel


Objectives For patients with recurrent/metastatic cervical cancer, incorporation of anti-angiogenesis therapy with chemotherapy yields a modest survival benefit of 3.7 months over chemotherapy alone (Tewari et al. NEJM. 2014). The rationale for checkpoint inhibition is supported by programmed death ligand-1 (PD-L1) expression in some cervical cancers (∼70%), with a higher proportion noted in squamous cell carcinoma vs adenocarcinoma. Based on the 14.3% objective response in KEYNOTE-158, the US FDA granted accelerated approval to pembrolizumab for PD-L1–positive cervical cancer for second-line therapy and beyond.

Methods KEYNOTE-826 is a phase 3, randomized, double-blind, placebo-controlled, multinational trial of chemotherapy with pembrolizumab or placebo for first-line treatment of recurrent, persistent, or metastatic cervical cancer. Patients not previously treated with chemotherapy for recurrence and not amenable to curative treatment will be randomized 1:1 to chemotherapy + pembrolizumab 200 mg or placebo every 3 weeks. The chemotherapy regimen (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5, with or without bevacizumab 15 mg/kg) will be selected by investigators pre-randomization. Stratification factors include metastatic status at diagnosis (yes/no), bevacizumab use (yes/no), and tumor PD-L1 status (combined positive score <1, 1 to <10, or ≥10). Treatment will continue until disease progression, unacceptable toxicity, or voluntary patient withdrawal for up to 35 cycles (∼2 years). Primary endpoints are progression-free survival (PFS) per RECIST v1.1 assessed by blinded independent central review and overall survival. Secondary endpoints are objective response, duration of response, 12-month PFS, patient-reported quality of life, and safety. Enrollment is ongoing globally. identifier: NCT03635567.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.