217O - Pembrolizumab (pembro) combination therapies in patients with metastatic castration-resistant prostate cancer (mCRPC): Cohorts A-C of the phase Ib/II KEYNOTE-365 study

Background

Pembro had antitumor activity as monotherapy in patients (pts) with mCRPC. KEYNOTE-365 (NCT02861573) evaluated safety and efficacy of pembro as combination therapy in pts with mCRPC. Findings for cohorts A, B, and C are reported with extended follow-up.

Methods

In this nonrandomized, multicohort, open-label phase Ib/II trial, pts with mCRPC were administered pembro (200 mg IV Q3W) in combination with olaparib (400-mg capsule or 300-mg tablet BID) if pretreated with docetaxel (cohort A); docetaxel (75 mg/m² IV Q3W) + prednisone (5 mg orally BID) if pretreated with abiraterone acetate or enzalutamide (enza; cohort B); or enza (160 mg/day orally) if pretreated with abiraterone acetate (cohort C). Primary end points: PSA response rate (confirmed PSA decrease ≥50%), ORR by blinded independent central review and safety.

Results

With a database cutoff of June 24, 2019, 84 (cohort A), 104 (cohort B), and 102 (cohort C) pts began treatment; median time from enrollment to data cutoff was 3.6, 19.9, and 19.1 mo, respectively; for pts with ≥27 wk of follow-up, it was 26.7, 21.8, and 21.4 mo. PSA response occurred in 9%, 28%, and 22% of pts in cohorts A, B, and C, respectively. ORR per RECIST v1.1 in pts with measurable disease and ≥27 wk of follow-up was 8% (2 PR), 18% (7 PR), and 12% (2 CR, 1 PR) for cohorts A, B, and C, respectively. Median rPFS was 4.3, 8.3, and 6.1 mo and median OS was 14.4, 20.4, and 20.4 mo in cohorts A, B, and C, respectively. Additional analyses are displayed in the table. In cohorts A, B, and C, grade ≥3 treatment-related adverse events (TRAEs) occurred in 35%, 40%, and 39% of pts, respectively. Two pts in cohort A (1 myocardial infarction, 1 cause unknown), 2 in cohort B (pneumonitis), and 1 in cohort C (cause unknown) died of TRAEs.

Conclusions

All 3 pembro combinations had antitumor activity against mCRPC, with a tolerability profile consistent with individual profiles of each agent. Phase III studies of these combinations is ongoing. Table: 217O

Efficacy outcomes

^aWith ≥27 wk potential follow-up.

Clinical trial identification

NCT02861573, August 10, 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

A.M. Joshua: Research grant/Funding (self): Bristol-Myers Squibb, Janssen Oncology, Merck Sharp & Dohme, Aptevo Therapeutics, Mayne Pharma, Roche/Genentech, Bayer, Macrogenics, Lilly. H. Gurney: Advisory/Consultancy: BMS, MSD, Pfizer, AstraZeneca, Ipsen, Roche. P.C.C. Fong: Advisory/Consultancy: MSD, Pfizer; Travel/Accommodation/Expenses: Pfizer. N.D. Shore: Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen, Astellas, AstraZeneca, Bayer, BMS, Dendreon, Ferring, Fergene, Janssen, Merck, MDxHealth, Myovant, Nymox, Pfizer, Sanofi-Genzyme, Tolmar; Speaker Bureau/Expert testimony: Bayer, Janssen, Pfizer, Astellas. E. Romano: Research grant/Funding (self): BMS, AZ; Travel/Accommodation/Expenses: AZ, Merck/MSD, Roche. M. Augustin: Advisory/Consultancy: Bristol-Myers Squibb, MSD, Pfizer, PharmaMar, Ipsen, AstraZeneca; Travel/Accommodation/Expenses: Lilly, Novartis, Bristol-Myers Squibb, PharmaMar, Ipsen; Research grant/Funding (institution): Bristol-Myers Squibb, MSD, Morphosys, AstraZeneca, Pfizer, PharmaMar. J.M. Piulats: Advisory/Consultancy: Roche, Novartis, Jansen, Astellas, Bayer, Sanofy-Genzyme, MSD, BMS, Merk-Serono, Clovis, AstraZeneca, Beigene, VCN Biotech; Research grant/Funding (self): Roche, Jansen, Astellas, MSD, BMS, Merk Serono, AstraZeneca, Beigene, VCN Biotech; Travel/Accommodation/Expenses: Roche, Astellas, Jansen. W.R. Berry: Research grant/Funding (self): Merck, Pfizer; Advisory/Consultancy: Pfizer, Genomic Health. M.P. Kolinsky: Honoraria (self): Janssen, Astellas, Bayer; Advisory/Consultancy: Janssen, Ipsen, BMS, AZ, Merck; Travel/Accommodation/Expenses: Novartis. S.S. Sridhar: Advisory/Consultancy: Merck, Pfizer, Roche, BMS, Janssen, Astellas, AstraZeneca, Bayer. H.J. Conter: Full/Part-time employment: Hoffman-La Roche Canada; Advisory/Consultancy: Janssen, Roche; Travel/Accommodation/Expenses: Bayer. T. Todenhöfer: Advisory/Consultancy: Amgen, Astellas, AstraZeneca, Bayer, BMS, Ipsen, Janssen, MSD, Roche, Sanofi. L.J. Appleman: Research grant/Funding (institution): Acerta, Agensys, Astellas, Aveo, Bayer, Bristol-Myers Squibb, Calithera, Esai, Exelixis, Genentech, Inovio, Novartis, Eli Lilly, Merck, Peloton, Tokai. H. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. C. Schloss: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. C.H. Poehlein: Leadership role, 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 Biosystem, Daiichi Sankyo, Sierra Oncology, Bayer, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim, Celgene, Taiho Pharmaceuticals, Genmab, GlaxoSmit; Research grant/Funding (self): AstraZeneca, Genentech, Sanofi, Taiho Pharmaceuticals, Daiichi Sankyo, Merck Serono, Astex Pharmaceuticals, Merck Sharp & Dohme, Orion Pharma, GlaxoSmithKline, Cellcentric, Celgene, Sierra Oncology, Bayer, MedImmune, Medivation, Terumo, Astellas Pharma, G. E.Y. Yu: Honoraria (institution): AbbVie, Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, Clovis, Dendreon, EMD Serono, Incyte, Janssen, Merck, Pharmacyclics, QED, Sanofi Genzyme, Seattle Genetics, Tolmar; Advisory/Consultancy: AbbVie, Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, Clovis, Dendreon, EMD Serono, Incyte, Janssen, Merck, Pharmacyclics, QED, Sanofi Genzyme, Seattle Genetics, Tolmar; Research grant/Funding (institution): Daiichi-Sankyo, Dendreon, Merck, Pharmacyclics, Seattle Genetics, Taiho. All other authors have declared no conflicts of interest.