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

Abstract

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/m + cisplatin 50 mg/m 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.