Abstract CT162: Pembrolizumab monotherapy for the adjuvant treatment of renal cell carcinoma post-nephrectomy: Randomized, double-blind, Phase III KEYNOTE-564 study
Authors: Choueiri Toni K. , Quinn David I. , Zhang Tian , Gurney Howard , Doshi Gurjyot K. , Cobb Patrick Wayne , Parnis Francis , Lee Jae-Lyun , Park Se Hoon , Semenov Andrey , Thiery-Vuillemin Antoine , Sawrycki Piotr , Tomczak Piotr , Alekseev Boris , Izmailov Adel , Chang Wayne Yen-Hwa , Wan Shuyan M. , Poehlein Christian Heinrich , Willemann-Rogerio Jaqueline , Powles Thomas 
Published: August 2019

Abstract
Background: Typical management for renal cell carcinoma (RCC) is nephrectomy. However, patients with intermediate- to high-risk advanced disease can experience relapse. Upregulation of the programmed death 1 (PD-1) pathway is associated with poor prognosis in RCC, and drugs to target the PD-1 pathway have shown efficacy and reasonable safety in metastatic RCC. Therefore, the PD-1 pathway may represent a novel target to prevent disease recurrence in the adjuvant setting. The randomized, double-blind, placebo-controlled, phase 3 KEYNOTE-564 trial (ClinicalTrials.gov identifier, NCT03142334) is designed to evaluate the efficacy and safety of pembrolizumab in the adjuvant treatment of RCC after nephrectomy.
Trial Design: Patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg or placebo every 3 weeks by intravenous infusion. Treatment will continue until disease recurrence, treatment discontinuation, or the completion of 17 cycles. Randomization will be stratified by metastasis stage (M0 vs M1 NED). Randomization within the M0 group will be further stratified by Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 and region (US vs rest of world). Imaging will be performed every 12 weeks after randomization, every 12 weeks for the first year of follow-up, every 16 weeks during years 2 to 4 of follow-up, and every 24 weeks thereafter. Key inclusion criteria are age ≥18 years; histologically confirmed clear cell RCC of intermediate-high risk (pT2, grade 4 or sarcomatoid, N0 M0; pT3, any grade, N0 M0), high risk (pT4, any grade, N0 M0; pT any stage, any grade, N+ M0), or M1 NED; no prior systemic therapy for advanced RCC; partial nephroprotective or radical complete nephrectomy with negative surgical margins; disease free after partial or radical complete nephrectomy validated by either computed tomography or magnetic resonance imaging; ECOG PS 0 or 1; and adequate and available tumor sample for biomarker analyses. Primary end point is disease-free survival (DFS) per investigator assessment. Secondary end point is overall survival (OS). Additional secondary analyses are safety and tolerability, pharmacokinetic parameters, antidrug antibodies, patient-reported outcomes, and DFS and OS per PD-L1 expression status. Biomarkers associated with response will be evaluated as an exploratory objective. KEYNOTE-564 is underway in 19 countries in Asia, Australia, Europe, North America, and South America, and recruitment will continue until ~950 patients are enrolled.
Citation Format: Toni K. Choueiri, David I. Quinn, Tian Zhang, Howard Gurney, Gurjyot K. Doshi, Patrick Wayne Cobb, Francis Parnis, Jae-Lyun Lee, Se Hoon Park, Andrey Semenov, Antoine Thiery-Vuillemin, Piotr Sawrycki, Piotr Tomczak, Boris Alekseev, Adel Izmailov, Wayne Yen-Hwa Chang, Shuyan M. Wan, Christian Heinrich Poehlein, Jaqueline Willemann-Rogerio, Thomas Powles. Pembrolizumab monotherapy for the adjuvant treatment of renal cell carcinoma post-nephrectomy: Randomized, double-blind, Phase III KEYNOTE-564 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT162.