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

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