LAUSR

Abstract Background In mCRPC pts unselected for homologous recombination deficiency (HRD), promising activity was seen with combination programmed death 1 inhibitor pembro and OLA in the phase 1b/2 KEYNOTE-365 study (NCT02861573), warranting further investigation in this population. KEYLYNK-010 (NCT03834519) is a phase 3, randomized, open-label trial to evaluate efficacy and safety of pembro plus OLA in molecularly unselected ENZA- or ABI-pretreated pts with mCRPC whose disease progressed with CTx. Trial design Eligible pts (≥18 years) must have histologically confirmed mCRPC and prior treatment (tx) with ABI or ENZA (but not both) and prior tx with CTx (1 prior docetaxel-based regimen). Pts must have an ECOG PS of 0/1, adequate organ function, and tumor tissue for biomarker analysis. Pts will be randomly assigned 2:1 to receive pembro 200 mg intravenously Q3W plus OLA 300 mg orally twice daily or ABI 1000 mg orally once daily plus prednisone/prednisolone 5 mg orally twice daily (for ENZA-pretreated pts) or ENZA 160 mg/day orally (for ABI-pretreated pts). Arms will be stratified per prior tx (ABI/ENZA) and presence of measurable disease (yes/no). Responses will be assessed by CT/MRI and radionuclide bone imaging per PCWG-modified RECIST v1.1 by blinded independent central review (BICR) Q9W during the first year and Q12W thereafter. Tx will continue with up to 2 years of pembro (35 cycles) and OLA or ABI/ENZA until radiographic disease progression, unacceptable toxicity, or consent withdrawal. Primary end points are overall survival and radiographic progression-free survival. The key secondary efficacy end point is time to initiation of subsequent anticancer therapy or death. Other secondary end points are objective response rate and duration of response per PCWG-modified RECIST v1.1 by BICR, time to first symptomatic skeletal event, and safety and tolerability. Prognostic or predictive molecular biomarkers (eg, genomic HRD status) will be explored. Approximately 780 pts will be enrolled. Clinical trial identification NCT03834519; February 8, 2019. Editorial acknowledgement Medical writing and/or editorial assistance was provided by Matt 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. Disclosure E. Yu: Advisory / Consultancy: Merck, Bayer, Amgen, Pharmacyclics, Seattle Genetics; Research grant / Funding (self): Merck, Agensys, Dendreon, Seattle Genetics, Taiho, Daiichi-Sankyo; Travel / Accommodation / Expenses: Merck, Bayer, Amgen, Pharmacyclics, Seattle Genetics. J. Kim: Full / Part-time employment: Merck & Co., Inc.; Shareholder / Stockholder / Stock options: Merck & Co., Inc. E.S. Antonarakis: Honoraria (self), Research grant / Funding (self): Janssen, Sanofi, Dendreon, AstraZeneca, Clovis, Merck; Advisory / Consultancy: Astellas, Medivation, ESSA, Eli Lilly; Research grant / Funding (self): Johnson & Johnson, Genentech, Novartis, BMS; Non-remunerated activity/ies, Patent holder: Qiagen. All other authors have declared no conflicts of interest.