922TiP - KEYNOTE-564: Phase 3 trial of pembrolizumab in the adjuvant treatment of renal cell carcinoma (RCC)

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Renal Cell Cancer
Cancer Immunology and Immunotherapy
Genitourinary Cancers
Presenter Toni Choueiri
Citation Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371
Authors T.K. Choueiri1, T. Powles2, T. Zhang3, D.I. Quinn4, J.E. Gschwend5, S.S. Wan6, C. Poehlein6
  • 1Genitourinary Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 2Centre For Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London/GB
  • 3Oncology, Duke Cancer Center, Durham/US
  • 4Gu Oncology, USC Norris comprehensive cancer center, 90033 - los angeles/US
  • 5Oncology, Technical University of Munich, Munich/DE
  • 6Medical Oncology, Merck & Co., Inc., Kenilworth/US

Abstract

Background

Effective adjuvant therapies for patients (pts) with RCC at risk of recurrence after nephrectomy are lacking. Programmed death ligand 1 (PD-L1) and 2 (PD-L2) expression predicts poor prognosis in RCC. Programmed death 1 (PD-1) inhibitors have demonstrated activity in metastatic RCC, and PD-1 may represent a novel therapeutic target in the adjuvant setting. Pembrolizumab is a PD-1 inhibitor that directly blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This randomized, double-blind, placebo-controlled phase 3 trial will evaluate the efficacy and tolerability of pembrolizumab as adjuvant therapy in pts with RCC who have T2 grade 4, T3, T4, N (+), or stage M1 with no evidence of disease (M1 NED) following nephrectomy and/or metastasectomy (NCT03142334).

Trial design

Key inclusion criteria are: age ≥18 years; histologically confirmed RCC with a clear cell component; intermediate-high or high risk of recurrence, or M1 NED; no prior systemic therapy for advanced RCC; disease-free following complete or partial nephrectomy (and metastasectomy in M1 NED pts) with negative surgical margins; and Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Approximately 950 pts will be randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg every 3 weeks by intravenous infusion, or placebo, continued for up to 17 cycles (∼1 year) or until disease recurrence or treatment discontinuation. Randomization will be stratified by metastasis stage (M0 vs M1 NED); within the M0 group, randomization will be further stratified by ECOG performance status (0 vs 1) and region (US vs rest of world). The primary end point is investigator-assessed disease-free survival (DFS). Radiographic imaging will be performed every 12 weeks. Secondary objectives include overall survival (OS), safety, disease recurrence-specific survival, DFS and OS according to PD-L1 expression status, pharmacokinetics, antidrug antibodies, and patient-reported outcomes. Molecular biomarkers that may be associated with response, safety, pharmacodynamic activity, or mechanism of action will be evaluated as exploratory objectives.

Clinical trial identification

NCT03142334; May 3, 2017

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Disclosure

T.K. Choueiri: Ad Board and/or funding: AstraZeneca Bayer Bristol-Myers Squib Cerulean Eisai, Foundation Medicine Inc Genetech, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus Labs Inc, Roche, Eisai Exelixis GSK Merck, Tracon. T. Powles: Research Funding/Honoraria/Travel: Pfizer, Merck, AstraZeneca, Roche, Novartis T. Zhang: Owns stock in Capio Biosciences and have received research funding from Janssen, Pfizer, and Acerta. D.I. Quinn: Ad board/funding/honoraria: Pfizer, Bristol-Myers Squib, Merck, EMD Serono, AstraZeneca, Genentech, Exelixis. J.E. Gschwend: Ad board/Honoraria/Travel Expenses: Bayer, Bristol-Myers Squib, Janssen, Novartis, Pfizer, Roche. S.S. Wan: Employment and stock ownership: Merck & Co., Inc. C. Poehlein: Employment: Merck & Co/MSD.