Abstract 1389P
Background
Initial analysis of Cohort D of the phase 1b/2 KEYNOTE-365 (NCT02861573) study showed pembro + abi and prednisone had antitumor activity and acceptable safety in patients (pts) with chemotherapy-naive mCRPC. Two-year follow-up is presented.
Methods
Eligible pts had ECOG PS 0-1, disease progression ≤6 mo of screening, and no prior chemotherapy for mCRPC. Pts must not have received prior next-generation hormonal agents (NHAs) for mCRPC or were intolerant to or progressed on enzalutamide for mCRPC. Pts received pembro 200 mg IV Q3W + abi 1000 mg PO QD and prednisone 5 mg PO BID. Primary end points: safety, PSA response rate, and ORR per RECIST v1.1 blinded independent central review (BICR). Secondary end points: DOR and DCR (CR + PR + SD or non-CR/non-PD ≥6 mo) per RECIST v1.1 by BICR, rPFS per PCWG3-modified RECIST v1.1 by BICR, and OS.
Results
103 pts were treated; 35.9% had RECIST-measurable disease per BICR, 72.8% received no prior NHAs, and 26.2% received prior enzalutamide. Median time from first dose to data cut-off (02/14/22) was 28.2 mo (range, 20.2-37.6). Confirmed PSA response was 56.3% (58/103 pts). 78.6% had a PSA reduction from baseline (confirmed and unconfirmed). ORR for pts with RECIST-measurable disease was 16.2% (1 CR; 5 PRs): 21.7% in pts with no prior NHAs and 7.7% with prior enzalutamide. 2 pts with RECIST non-measurable disease had CR. Median DOR for all responders was not reached (range, 2.1+ to 24.4+). DCR for all pts was 44.7% in the overall population: 58.7% in pts with no prior NHAs and 7.4% with prior enzalutamide. Median rPFS was 15.1 mo (95% CI, 9.2-22.2); 24-mo rPFS was 33.3%. Median OS was 29.7 mo (95% CI, 23.3-NR); 36-mo OS was 49.5%. Treatment-related AEs occurred in 91.3% of pts; grade 3-5 occurred in 38.8%. Overall, 18.4% and 12.6% of pts had a grade 3/4 ALT or AST elevation, respectively. 1 pt died due to treatment-related myasthenic syndrome.
Conclusions
With an additional 10.6 mo of follow-up, pembro + abi and prednisone continued to show antitumor activity and acceptable safety in pts with chemotherapy-naive mCRPC. There was an increased incidence of grade 3/4 ALT/AST elevations than reported for individual agents.
Clinical trial identification
NCT02861573, Release Date: August 10, 2016.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Jemimah Walker, PhD and Matthew Grzywacz, PhD of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
M. Linch: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, BioNTech, Pfizer, Janssen; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, BioNTech, Pfizer; Financial Interests, Institutional, Research Grant: Shionogi Ltd.; Financial Interests, Institutional, Principal Investigator: Shionogi Ltd.; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Astellas, ADC Therapeutics, Bristol Myers Squibb; Financial Interests, Personal, Principal Investigator: Astellas, Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board: Bicycle Therapeutics; Financial Interests, Personal, Research Grant: Bristol Myers Squibb. C. Ferrario: Financial Interests, Personal, Other, Honoraria: Pfizer, Bayer, Novartis, AstraZeneca, Merck, Astellas Pharma, Roche Pharma; Financial Interests, Personal, Advisory Board: Genomic Health, Merck, AstraZeneca, Bayer, Odonate Therapeutics; Financial Interests, Personal, Speaker’s Bureau: Merck, Janssen; Financial Interests, Personal, Other, Travel expenses: Novartis, Roche; Financial Interests, Personal, Research Grant: Bayer, Astellas Pharma, AstraZeneca, Eli Lilly, Merck, Novartis, Roche/Genentech, Sanofi, Janssen Oncology, Zymeworks, Seattle Genetics, Immunomedics, Bicycle Therapeutics, Sermonix Pharmaceuticals; Financial Interests, Personal, Funding: Bayer, Astellas, AstraZeneca, Eli Lilly, Merck, Novartis, Roche/Genentech, Sanofi, Janssen Oncology, Zymeworks, Seattle Genetics, Immunomedics, Bicycle Therapeutics, Sermonix Pharmaceuticals. B. Laguerre: Financial Interests, Personal, Other, Honoraria: AstraZeneca, BMS, Ipsen, Roche, Astellas, Janssen, Pfizer; Financial Interests, Personal, Other, Travel expenses: Pfizer, Janssen. J.A. Arranz Arija: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Eisai, Merck, MSD, Pfizer; Non-Financial Interests, Institutional, Principal Investigator: BMS. T. Todenhöfer: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Amgen, Bayer, BMS, Ipsen, Janssen, MSD, Pfizer, Roche. P.C. Fong: Financial Interests, Personal, Advisory Board: MSD, Pfizer. J.M. Piulats Rodriguez: Financial Interests, Personal, Advisory Board: MSD, Janssen, BMS, Roche, Astellas, Bayer, BeiGene, VCN, Immunocore; Financial Interests, Personal, Research Grant: MSD, Janssen, BeiGene, Novartis; Financial Interests, Personal, Funding: MSD, Janssen, BeiGene, Novartis. W. Berry: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Speaker’s Bureau: Dendreon. U. Emmenegger: Financial Interests, Personal, Advisory Board: Amgen, Astellas, AstraZeneca, Bayer, Ferring, Janssen, Knight, Merck, Novartis (Endocyte/AAA), Pfizer; Financial Interests, Personal, Research Grant: Astellas, Bayer, Janssen; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Bayer, Janssen, Merck, Novartis (Endocyte/AAA), Point Biopharma, Roche-Genentech; Financial Interests, Institutional, Principal Investigator: Astellas, AstraZeneca, Bayer, Janssen, Merck, Novartis (Endocyte/AAA), Point Biopharma, Roche-Genentech. L. Mourey: Financial Interests, Personal, Other, Honoraria: Sanofi, Astellas, Janssen, Ipsen, BMS, AstraZeneca, Pfizer, MSD; Financial Interests, Personal, Advisory Board: Astellas, Sanofi, BMS, Janssen; Financial Interests, Personal, Other, Travel expenses: Astellas, Sanofi, Janssen, Ipsen, BMS, AstraZeneca, Pfizer, MSD. N. Mar: Other, Personal, Speaker’s Bureau: Seattle Genetics, Eisai. L.J. Appleman: Financial Interests, Institutional, Sponsor/Funding: Merck. A. Joshua: Non-Financial Interests, Personal, Principal Investigator: Janssen, Merck. H.J. Conter: Financial Interests, Personal, Other, Honoraria: Agendia; Financial Interests, Personal, Full or part-time Employment: Hoffman La Roche. X.T. Li: Financial Interests, Personal, Full or part-time Employment: MSD. C. Schloss: Financial Interests, Personal, Full or part-time Employment: Merck. C.H. Poehlein: Financial Interests, Personal, Full or part-time Employment: Merck. J.S. de Bono: Financial Interests, Personal, Advisory Board: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi, Eisai, Genentech Roche, Genmab, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals; Financial Interests, Institutional, Advisory Board: Harpoon; Financial Interests, Institutional, Research Grant: 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, Crescendo Biologics; Non-Financial Interests, Principal Investigator: 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, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals; Non-Financial Interests, Institutional, Product Samples: Daiichi, Bayer, Pfizer, Merck Serono, AstraZeneca, Harpoon, Sierra Oncology, Genentech/Roche, Sanofi Aventis, GlaxoSmithKline. E.Y. Yu: Financial Interests, Personal, Advisory Board: Janssen, Bayer, Seattle Genetics, Clovis Oncology, Advanced Accelerator Applications, Sanofi, AbbVie, Myovant Sciences; Financial Interests, Personal, Research Grant: Dandreon, Seattle Genetics, Daiichi Sankyo, Taiho Pharmaceutical, Blue Earth Diagnostics, Bayer; Financial Interests, Personal, Funding: Dandreon, Seattle Genetics, Daiichi Sankyo, Taiho Pharmaceuticals, Blue Earth Diagnostics, Bayer. All other authors have declared no conflicts of interest.