ASCO GU 2018: Phase III, Randomized, Double-blind Trial of Pembrolizumab in the Adjuvant Treatment of RCC: KEYNOTE-564

San Francisco, CA ( Dr. David Quinn presented the trial design for KEYNOTE-564 today at the GU ASCO 2018 poster session. KEYNOTE-564 is a phase III, randomized, double-blind trial of pembrolizumab in the adjuvant treatment of renal cell carcinoma (RCC). Many patients with intermediate- to high-risk advanced RCC will progress within three years following nephrectomy. Given the underwhelming trials assessing adjuvant tyrosine kinase inhibitors (TKIs) [1-3], novel treatments in the adjuvant setting are needed to prevent disease recurrence in these higher-risk patients. Upregulation of the programmed death 1 (PD-1) pathway is associated with more aggressive disease and poor prognosis. PD-1 inhibitors have demonstrated activity in metastatic RCC, and PD-1 may represent a novel therapeutic target in the adjuvant setting. Pembrolizumab, a PD-1 inhibitor, blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

Trial Design: KEYNOTE-564 is a randomized, double-blind, placebo-controlled phase III trial designed to evaluate the efficacy and safety of pembrolizumab as adjuvant therapy in patients with RCC. Eligibility criteria include age ≥18 years, intermediate- to high-risk (T2 grade 4, T3), high-risk (T4), or M1 with no evidence of disease RCC with a clear cell component, no prior systemic therapy for advanced RCC, disease free following complete or partial nephrectomy (and metastasectomy in patients with M1 no evidence of disease) with negative surgical margins, ECOG PS 0/1, and provision of a tumor sample for biomarker analyses. Patients will be randomly assigned (1:1) to pembrolizumab 200 mg administered IV every 3 weeks or placebo. Randomization will be stratified by metastasis stage (M0 vs M1 no evidence of disease); within the M0 group, randomization will be further stratified by ECOG PS (0 vs 1) and region (US vs rest of world). Treatment will continue until disease recurrence, unacceptable toxicity, or the completion of 17 cycles (~1 year), and imaging will be performed every 12 weeks. The primary end point is disease-free survival (DFS) per investigator assessment. The key secondary end point is overall survival (OS). Other secondary objectives include safety, disease recurrence-specific survival, DFS and OS according to PD-L1 expression status, and patient-reported outcomes. Biomarkers that may be associated with response will be evaluated as an exploratory objective. Enrollment is ongoing and will continue until ~950 patients are enrolled.
Clinical trial information: NCT03142334

Speaker: David I. Quinn, USC Keck School of Medicine Norris Comprehensive Cancer Center, Los Angeles, CA

Co-Authors: Tian Zhang, Howard Gurney, Gurjyot K. Doshi, Patrick Wayne Cobb, Francis Parnis, Jae-Lyun Lee, Se Hoon Park, Andrey Semenov, Wayne Yen-Hwa Chang, Thomas Powles, Shuyan (Sabrina) Wan, Christian Heinrich Poehlein, Toni K. Choueiri

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md, at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA