Abstract 2241
Background
Treatment options for patients (pts) with mCRPC are noncurative, and life expectancy is only about 3 y. Enzalutamide plus the programmed death 1 (PD-1) inhibitor pembro showed activity in abiraterone-pretreated pts with mCRPC in the phase 1b/2 KEYNOTE-365 (NCT02861573) study. In another study (NCT02312557) some pts had profound anticancer response to pembro plus enzalutamide that lasted years. KEYNOTE-641 (NCT03834493) is a randomized phase 3 trial to evaluate efficacy and safety of pembro plus enzalutamide vs placebo plus enzalutamide for pts with mCRPC.
Trial design
Adults (≥18 y) with histologically or cytologically confirmed prostate cancer and mCRPC with biochemical or radiographic progression are eligible. Pts who received chemotherapy for mCRPC, checkpoint inhibition, or any treatment with a second-generation androgen receptor inhibitor (eg, enzalutamide, apalutamide, or darolutamide) are excluded. Pts intolerant to or progressed on prior abiraterone therapy were included. Pts must have ECOG PS 0/1, adequate organ function, and tissue for biomarker analysis. Approximately 1200 pts will be randomly assigned 1:1 to receive enzalutamide 160 mg/d plus pembro 200 mg Q3W or enzalutamide 160 mg/d plus placebo. Treatment will be stratified per prior abiraterone treatment (yes/no), metastases (bone only/liver/other), and prior docetaxel treatment for metastatic hormone-sensitive prostate cancer (yes/no). Responses will be assessed by CT/MRI and radionuclide bone imaging per PCWG-modified RECIST v1.1 every 9 wk during the first year and every 12 wk thereafter. Treatment will continue with enzalutamide plus pembro/placebo until radiographic disease progression, unacceptable toxicity, or consent withdrawal, with a maximum of 2 yr of treatment for the pembro/placebo component of the combination. Primary end points: overall survival and radiographic progression-free survival by blinded independent central review. Key secondary efficacy end point is time to subsequent anticancer therapy or death; safety and tolerability will also be reported.
Clinical trial identification
NCT03834493; February 8, 2019.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Astellas is providing enzalutamide for this study.
Disclosure
J.N. Graff: Speaker Bureau / Expert testimony: CME activity for i3 Health; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Bristol-Myers Squibb. J. Burgents: Full / Part-time employment: Merck; Full / Part-time employment: AstraZeneca; Full / Part-time employment: Array BioPharma; Full / Part-time employment: Merrimack. L.W. Liang: Shareholder / Stockholder / Stock options, Full / Part-time employment: MSD. A. Stenzl: Advisory / Consultancy: Ipsen Pharma, Sanofi Aventis, CureVac, Astellas; Research grant / Funding (institution): Johnson&Johnson, Roche, Cepheid, Amgen Inc, Bayer AG, CureVac, Immatics Biotechnology GmbH, GemeDX Biosciences, Immatics Biotechnologies GmbH, Novartis AG, Karl Storz AG; Speaker Bureau / Expert testimony: GBA; Non-remunerated activity/ies, Patents, but no royalties: No company.
Resources from the same session
5218 - Elevated driver mutational burden or number of perturbed pathways and poor response to abiraterone or enzalutamide in metastatic castration-resistant prostate cancer
Presenter: Bram De Laere
Session: Poster Display session 3
Resources:
Abstract
2452 - High proportion of multiple KRAS mutations in circulating tumor DNA and tumor tissue of pancreatic ductal adenocarcinoma
Presenter: Min Kyeong Kim
Session: Poster Display session 3
Resources:
Abstract
3328 - Biological difference of tumor mutational burden (TMB) and microsatellite instability (MSI) status in patients (pts) with somatic vs. germline BRCA1/2-mutated advanced gastrointestinal (GI) cancers using cell-free DNA (cfDNA) sequencing analysis in the GOZILA study
Presenter: Yasuyuki Kawamoto
Session: Poster Display session 3
Resources:
Abstract
3022 - Cell-Free DNA to Detect Focal Versus Non-Focal MET Amplification in Metastatic Colorectal Cancer Patients: Combined Analysis from Japan and the United States
Presenter: Mishima Saori
Session: Poster Display session 3
Resources:
Abstract
2833 - Presence of circulating tumor DNA in surgically resected renal cell carcinoma is associated with advanced disease and poor patient prognosis
Presenter: Andres Correa
Session: Poster Display session 3
Resources:
Abstract
1376 - Combined genomic and epigenomic assessment of cell-free circulating tumor DNA (cfDNA) for cancer diagnosis and recurrence-risk assessment in early-stage lung cancer
Presenter: Junghee Lee
Session: Poster Display session 3
Resources:
Abstract
4050 - DEMo: a prospective evaluation of a prognostic clinico-molecular composite score in NSCLC patients treated with immunotherapy.
Presenter: Arsela Prelaj
Session: Poster Display session 3
Resources:
Abstract
4727 - Bespoke circulating tumor DNA (ctDNA) analysis as a predictive biomarker in solid tumor patients (pts) treated with single agent pembrolizumab (P)
Presenter: Cindy Yang
Session: Poster Display session 3
Resources:
Abstract
3662 - Dynamic changes in whole-genome cell-free DNA (cfDNA) to identify disease progression prior to imaging in advanced solid tumors
Presenter: Andrew Davis
Session: Poster Display session 3
Resources:
Abstract
3817 - Evaluation of Microsatellite Instability Testing Through cell-free DNA sequencing
Presenter: Shile Zhang
Session: Poster Display session 3
Resources:
Abstract