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
3664 - Longitudinal changes in cell-free DNA (cfDNA) methylation levels identify early non-responders to treatment in advanced solid tumors
Presenter: Andrew Davis
Session: Poster Display session 3
Resources:
Abstract
3212 - Multigene panel testing results for hereditary breast cancer in 1325 individuals: implications for gene selection and considerations for guidelines.
Presenter: Georgios Tsaousis
Session: Poster Display session 3
Resources:
Abstract
2591 - PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors
Presenter: Julia Quintanilha
Session: Poster Display session 3
Resources:
Abstract
4377 - ERBB2 mRNA as a predictor in HER2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC) treated with HER2 blockade in combination with endocrine therapy (ET): a retrospective analysis of the ALTERNATIVE and SOLTI-PAMELA trials.
Presenter: Nuria Chic
Session: Poster Display session 3
Resources:
Abstract
3439 - Early on-treatment vs pre-treatment tumor transcriptomes as predictors of response to neoadjuvant therapy for HER2-positive inflammatory breast cancer
Presenter: Sonia Pernas
Session: Poster Display session 3
Resources:
Abstract
2512 - AXL expression predicts poor prognosis and lack of efficacy of anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC)
Presenter: Claudia Cardone
Session: Poster Display session 3
Resources:
Abstract
4061 - Prevalence of EGFR mutations and its correlation with Egyptian patients’ human kinetics (PEEK Study)
Presenter: Adel Ibrahim
Session: Poster Display session 3
Resources:
Abstract
2547 - Evaluation of tumor microenvironment identifies immune correlates of response to combination immunotherapy with margetuximab (M) and pembrolizumab (P) in HER2+ gastroesophageal adenocarcinoma (GEA)
Presenter: Sergio Rutella
Session: Poster Display session 3
Resources:
Abstract
4671 - Clinicopathological and molecular criteria assessment for the screening of hypermutated proficient mismatch repair (pMMR) colorectal cancers (CRC) with exonucleasic domain POLE (edPOLE) mutations (mt).
Presenter: Benoit Rousseau
Session: Poster Display session 3
Resources:
Abstract
3862 - Tumor mutation burden and microsatellite instability in colorectal cancer
Presenter: Francesca Fenizia
Session: Poster Display session 3
Resources:
Abstract