Background

Chemotherapy-naive patients (pts) with mCRPC who had disease progression with enza were enrolled in C4 and C5 of the multicohort phase II KEYNOTE-199 study (NCT02787005).

Methods

Pts who did or did not previously take abiraterone acetate were eligible if they developed resistance to enza after prior response. Cohorts were composed of pts who had RECIST-measurable (C4) or bone-predominant nonmeasurable (C5) disease. Pts received pembro 200 mg Q3W for up to 35 cycles + enza QD until progression, toxicity, or withdrawal. The primary end point was ORR per RECIST v1.1 by blinded independent central review in C4; DOR was also analyzed. Secondary end points (both cohorts) were DCR, rPFS, OS, time to cytotoxic chemotherapy, time to new anticancer therapy, and safety.

Results

A total of 126 pts (C4, 81; C5, 45) were treated. Median (range) time from enrollment to data cutoff was 15 mo (7-21) and 19 mo (7-21) in C4 and C5, respectively. In C4, ORR (95% CI) was 12% (6-22) (2 CRs, 8 PRs) and median (range) DOR was 6.3 mo (2.5+ to 13.4); 4 responders (73% by Kaplan-Meier estimation) had a response ≥6 mo (Table). Median time to cytotoxic chemotherapy was 11.1 and 11.3 mo in C4 and C5, and time to PSA progression was 4.2 mo in both cohorts (Table). A total of 26% and 24% of pts in C4 and C5, respectively, experienced grade ≥3 treatment-related adverse events (TRAEs). Two pts in C4 died of immune-related AEs (Miller Fisher syndrome and myasthenia gravis). Incidence of any-grade/grade 3 or 4 rash (33%/6%), regardless of treatment relatedness, was higher than previously reported for individual agents but manageable with standard-of-care treatments. Table: 227P

Efficacy outcomes

Conclusions

After enza resistance, pembro + enza showed antitumor activity and manageable safety for RECIST-measurable and bone-predominant mCRPC. Pembro + enza is being evaluated in the ongoing phase III KEYNOTE-641 trial (NCT03834493)..

Clinical trial identification

NCT02787005, June 1, 2016.

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.

Disclosure

U.N. Vaishampayan: Advisory/Consultancy, Research grant/Funding (self): Merck & Co., Inc. T. Elliott: Research grant/Funding (self), Research grant/Funding (institution): Per-patient payments, Pfizer, Bayer, Astellas, AstraZeneca, Janssen, Travel/Accommodation/Expenses: Janssen. A.G. Omlin: Advisory/Consultancy: Astellas, Bayer, Sanofi, Roche, Janssen, MSD, Molecular Partners; Speaker Bureau/Expert testimony: Astellas, Janssen, Bayer; Travel/Accommodation/Expenses: Astellas, Bayer, Sanofi, Janssen; Research grant/Funding (institution): Teva, Janssen. J.N. Graff: Advisory/Consultancy: Sanofi, Astellas, Bayer, Valeant, Janssen; Travel/Accommodation/Expenses: Sanofi, Clovis, Janssen, Bayer. C.J. Hoimes: Honoraria (self): BMS, Genentech, Seattle Genetics; Advisory/Consultancy: Seattle Genetics, Merck, 2bPrecise; Speaker Bureau/Expert testimony: BMS, Genentech, Seattle Genetics, Eisai; Research grant/Funding (institution): Merck, Seattle Genetics, Genentech, Novartis, Astellas; Travel/Accommodation/Expenses: Sanofi, Clovis, Janssen, Bayer. S.T. Tagawa: Honoraria (self): Sanofi, Medivation/Astellas, Dendreon, Janssen, Genentech, Bayer, Endocyte, Eisai, Immunomedics, Karyopharm, AbbVie, Tolmar, Seattle Genetics, Amgen, Clovis, QED, Pfizer, AAA/Novartis, Genomic Health, Point Pharma, Ambrx; Research grant/Funding (institution): Sanofi, Medivation, Astellas, Janssen, Amgen, Progenics, Dendreon, Lilly, Genentech, Newlink, BMS, Inovio, AstraZeneca, Immunomedics, Aveo, Rexahn, Atlab, Boehringer Ingelheim, Millennium, Bayer, Merck, AbbVie, Karyopharm, Endocyte, Clovis, Seattle Geneti; Travel/Accommodation/Expenses: Amgen, Sanofi, Immunomedics. R.S. McDermott: Advisory/Consultancy: Bristol-Myers Squibb, Merck, Genentech/Roche, Pfizer Exelixix, Novartis, Array BioPharma, Peloton Therapeutics, EMD Serono, Jounce Therapeutics, Alkermes, Lilly, Eisai; Research grant/Funding (institution): Prometheus Laboratories, Bristol-Myers Squibb, Merck, Genentech, Novartis, Alkermes, Peloton Therapeutics; Honoraria (self), Other: BIDMC; Non-remunerated activity/ies: X4 Pharmaceuticals, AVEO. W.R. Gerritsen: Advisory/Consultancy: BMS, Iqvia, Bayer, MSD, Sanofi, Janssen-Cilag; Speaker Bureau/Expert testimony: MSD; Research grant/Funding (self): Astellas, Bayer, Janssen-Cilag, Sanofi. H. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. J. Kim: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. C. Schloss: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. J.S. de Bono: Advisory/Consultancy: AstraZeneca, Sanofi, Astellas Pharma, Pfizer, Genentech/Roche, Janssen Oncology, Menarini Silicon Biosystems, Daiichi Sankyo, Sierra Oncology, Bayer, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim, Celgene, Taiho Pharmaceuticals, Genmab, GlaxoSmi; Research grant/Funding (institution): AstraZeneca, Genentech, Sanofi, Taiho Pharmaceutcials, Daiichi Sankyo, Merck Serono, Astex Pharmaceuticals, Merck Sharp & Dohme, Orion Pharma, GlaxoSmithKline, Cellcentric, Celgene, Sierra Oncology, Bayer, MedImmune, Medivation, Terumo, Astellas Pharma, G. E.S. Antonarakis: Research grant/Funding (self): Janssen, Sanofi, Dendreon, AstraZeneca, Clovis, Merck, JohnsonJohnson, Genentech, Novartis, Bristol-Myers Squibb, Tokai, Celgene; Advisory/Consultancy: Janssen, Astellas, Sanofi, Dendreon, Medivation, ESSA, AstraZeneca, Clovis, Merck, Lilly, Amgen, Bayer, GlaxoSmithKline; Licensing/Royalties: Qiagen. All other authors have declared no conflicts of interest.