Abstract 612P
Background
Data from the phase I/II KEYNOTE-365 study (NCT02861573) showed antitumor activity and acceptable safety of pembro + olaparib in pts with molecularly unselected, docetaxel-pretreated mCRPC enrolled in cohort A. Updated results are reported for all pts after a minimum of 11.4 mo of follow-up.
Methods
In cohort A, pts with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo before screening received pembro 200 mg IV Q3W + olaparib 400-mg capsule or 300-mg tablet orally BID. Pts could have received 1 chemotherapy other than docetaxel for mCRPC and ≤2 second-generation androgen receptor–targeted therapies. Primary end points were PSA response rate (decrease of ≥50% from baseline), ORR by RECIST v1.1 by BICR, and safety. Secondary end points were DCR by BICR (CR or PR of any duration + SD or non-CR/non-PD ≥6 mo), DOR by BICR, rPFS by PCWG3, and OS.
Results
Of 104 enrolled pts, 102 were treated. Median follow-up, defined as time from enrollment to data cutoff, was 19.3 mo (range, 11.4-45.9). Confirmed PSA response rate in pts with a baseline PSA measurement (N = 102) was 14.7% (95% CI, 8.5-23.1). In 58 pts with measurable disease, confirmed ORR was 6.9% (95% CI, 1.9-16.7; 4 PRs). Median DOR was not reached (range, 7.2+ to 37.8+ mo); 2 pts had a response ≥12 mo. The DCR was 26.5% (95% CI, 18.2-36.1). Median rPFS was 5.2 mo (95% CI, 4.1-6.5); 12-mo rate was 28.8%. Median OS was 14.4 mo (95% CI, 10.4-17.9); 12-mo rate was 55.9%. Treatment-related AEs (TRAEs) occurred in 93 pts (91.2%); most frequent (≥30%) were anemia (41.2%), nausea (41.2%), decreased appetite (30.4%), and fatigue (30.4%). Grade 3-5 TRAEs occurred in 49 pts (48.0%). Six pts (5.9%) died of AEs; 2 deaths were treatment related (unknown cause and myocardial infarction).
Conclusions
With a minimum of 11.4 mo of follow-up, pembro + olaparib continued to show modest activity in pts with molecularly unselected, docetaxel-pretreated mCRPC. Safety was consistent with individual profiles of each agent. This combination is being evaluated further in the phase III KEYLYNK-010 study (NCT03834519).
Clinical trial identification
NCT02861573, August 10, 2016.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of ApotheCom (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: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Janssen, Bayer, Merck, Seattle Genetics, Clovis Oncology, Advanced Accelerator Applications, Sanofi, AbbVie, Myovant Sciences; Financial Interests, Institutional, Funding: Dendreon, Merck, Seattle Genetics, Daiichi Sankyo, Taiho Pharmaceutical, Pharmacyclics, Blue Earth Diagnostics, Bayer. J.M. Piulats: Financial Interests, Personal, Advisory Role, Advisory/consultancy: Roche, Novartis, Jansen, Astellas, Bayer, Sanofy-Genzyme, MSD, BMS, Merck-Serono, Clovis, AstraZeneca, Beigene, VCN Biotech; Financial Interests, Personal, Research Grant, Research grant/funding: Roche, Jansen, Astellas, MSD, BMS, Merck-Serono, AstraZeneca, Beigene, VCN Biotech; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Roche, Astellas, Janssen. G. Gravis: Financial Interests, Personal, Advisory Role, Advisory/consultancy: BMS, Janssen, Pfizer, Alliance Merck-Pfizer, AAA; Financial Interests, Institutional, Speaker’s Bureau, Speaker Bureau/Expert Testimony: Astellas, MSD, Janssen, AMGEN, BMS, Sanofi; Financial Interests, Institutional, Research Grant, Research grant/funding: Janssen, BMS; Financial Interests, Personal, Other, Travel expenses, including accommodations: BMS, Janssen, Sanofi. P.C.C. Fong: Financial Interests, Personal, Advisory Role, Advisory/consultancy: MSD; Financial Interests, Personal, Other, Travel expenses, including accommodations: Pfizer. B. Laguerre: Financial Interests, Personal, Other, Honoraria: BMS, Astellas, Janssen, AstraZeneca; Financial Interests, Personal, Other, Travel expenses, including accommodations: Pfizer, Astellas, Novartis, Janssen. J.A. Arranz Arija: Financial Interests, Personal, Advisory Role, Advisory/consultancy: Jansen, Astellas, MSD, Merck, Roche, EUSA; Financial Interests, Personal, Other, Travel expenses, including accommodations: Roche, Astellas, Ipsen; Financial Interests, Personal, Research Grant, Research grant/funding: BMS (SOGUG). S. Oudard: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Merck, Sanofi, Novartis, BMS, Ipsen, Astellas, Janssen, Pfizer, Bayer; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: AstraZeneca, Merck, Sanofi, Novartis, BMS, Ipsen, Astellas, Janssen, Pfizer, Bayer; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: AstraZeneca, Merck, Sanofi, Novartis, BMS, Ipsen, Astellas, Janssen, Pfizer, Bayer; Financial Interests, Personal, Research Grant, Research Grant/Funding: AstraZeneca, Sanofi, BMS, Ipsen, Janssen, Pfizer, Bayer. C. Massard: Financial Interests, Personal, Advisory Role: Amgen, Astellas Pharma, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Celgene, Debiopharm Group, Genentech/Roche, Ipsen, Janssen, Lilly, MSD, Novartis, Pfizer, Sanofi, Orion, Taiho Pharmaceutical, Blueprit Medicines, Innate Pharma, PharmaMar, Faron P. J. Carles: Financial Interests, Personal, Advisory Role, Advisory/consultancy: Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Johnson & Johnson, MSD Oncology, Novartis (AAA), Pfizer, Roche, Sanofi; Financial Interests, Personal, Speaker’s Bureau, Speaker Bureau/Expert Testimony: Astellas Pharma, Bayer, Johnson & Johnson; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: BMS, Ipsen, Roche, AstraZeneca; Financial Interests, Personal, Research Grant, Research Grant/Funding: AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, Inc., Astellas Pharma, AstraZeneca AB, Aveo Pharmaceuticals Inc., Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics Inc., Boehringer Ingelheim España, S.A., Bristol-Myers Squibb Inte. M.P. Kolinsky: Financial Interests, Personal, Other, Honoraria: AZ, Astella, Bayer, BMS, Eisai, Ipsen, Janssen, Merck; Financial Interests, Personal, Advisory Role, Consulting or advisory role: AstraZeneca, Astella, Bayer, BMS, Eisai, Ipsen, Janssen, Merck. M. Augustin: Financial Interests, Personal, Advisory Role, Advisory/consultancy: Bristol-Myers Squibb, MSD, Pfizer, PharmaMar, Ipsen, AstraZeneca, Novartis, Bayer, Roche; Financial Interests, Personal, Other, Travel expenses, including accommodations: Lilly, Novartis, Bristol-Myers Squibb, PharmaMar, Ipsen, Pfizer; Financial Interests, Institutional, Research Grant, Research grant/funding: Bristol-Myers Squibb, MSD, Morphosys, AstraZeneca, Pfizer, PharmaMar, Ipsen, Exelixis. H. Gurney: Financial Interests, Personal, Advisory Role: BMS, AstraZeneca, MSD, Merck, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Pfizer, MSD. X.T. Li: Financial Interests, Personal, Full or part-time Employment: MSD. C.H. Poehlein: Financial Interests, Personal, Full or part-time Employment: Merck & Co.; Financial Interests, Personal, Leadership Role: Merck & Co.; Financial Interests, Personal, Stocks/Shares: Merck & Co. C. Schloss: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. J.S. de Bono: Financial Interests, Personal, Other, Honoraria: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi, Eisai, Genentech Roche, Genmab, GlaxoSmithKline, Harpoon, Janssen, Menarini Silicon Biosystems, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi, Eisai, Genentech Roche, Genmab, GlaxoSmithKline, Harpoon, Janssen, Menarini Silicon Biosystems, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi, Eisai, Genentech Roche, Genmab, GlaxoSmithKline, Harpoon, Janssen, Menarini Silicon Biosystems, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer; Financial Interests, Institutional, Research Grant, Research Grant/Funding: Astellas, AstraZeneca, Bayer, Cellcentric, Daiichi, Genentech Roche, Genmab, GlaxoSmithKline, Harpoon, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Sanofi Aventis, Sierra Oncology, Taiho, Vertex Pharmaceuticals. All other authors have declared no conflicts of interest.