Abstract 611P
Background
KEYNOTE-199 (NCT02787005) is a multicohort phase II study to evaluate pembro in mCRPC. Previous analysis of 3 cohorts of patients (C1: RECIST-measurable, PD-L1+; C2: RECIST-measurable, PD-L1−; C3: bone-predominant irrespective of PD-L1) who were previously treated with a next-generation hormonal agent (NHA) and docetaxel showed durable antitumor activity and a manageable safety profile with pembro. Updated efficacy and safety data with 4 years’ follow-up are presented.
Methods
Patients received pembro 200 mg Q3W for up to 35 doses until progression, unacceptable toxicity, or withdrawal of consent. The primary end point was ORR (CR + PR) per RECIST v1.1 by blinded independent central review. Secondary end points were DCR (CR + PR of any duration + SD/non-CR/non-PD ≥6 months), DOR, confirmed PSA response (≥50% reduction from baseline) rate, rPFS per PCWG-3-modified RECIST v1.1, OS, and safety.
Results
Of 258 treated patients (C1: 133; C2: 67; C3: 58); 6 (2.3%) completed treatment and 252 (97.7%) discontinued, primarily because of progressive disease. Median time from enrollment to data cutoff date was 48.1 months (range, 43.1-51.1). In patients with measurable disease, ORR was 6.0% (95% CI, 2.6-11.5; 4 CR, 4 PR) in C1 and 3.0% (95% CI, 0.4-10.4; 2 PR) in C2. Median DOR was not reached in C1 or C2, but 3 pts in C1 continued in response for ≥36 months. Additional efficacy analyses are displayed in the table. Of all patients, treatment-related AEs occurred in 61.2% (158/258), and grade 3-5 treatment-related AEs occurred in 15.9% (41/258). One patient in each cohort died of a treatment-related AE (C1: sepsis; C2: unknown; C3: immune-related pneumonitis).
Conclusions
After 4 years’ follow-up, pembro monotherapy still showed modest antitumor activity and a manageable safety profile in patients with docetaxel-pretreated mCRPC. Table: 611P
| Cohort 1 N=133 | Cohort 2 N=67 | Cohort 3 N=58 | |
| ORR, n/N (%) | 8/133 (6.0) | 2/67 (3.0) | NA |
| DCR, n/N (%) | 13/133 (9.8) | 3/67 (4.5) | 12/58 (20.7) |
| DOR, range, mo | 1.9 to 49.0+ | 4.4 to 35.3+ | NA |
| PSA response rate in pts with baseline PSA, n/N (%) | 8/124 (6.5) | 5/61 (8.2) | 1/58 (1.7) |
| Time to PSA progressiona | N=133 | N=67 | N=58 |
| Median (95% CI), mo | 5.1 (4.2-NR) | 6.2 (4.2-6.9) | 4.2 (4.2-4.6) |
| 36-month rate, % (95% CI) | 38.3 (21.6-54.8) | NA | NA |
| rPFSa | |||
| Median (95% CI), mo | 2.1 (2.0-2.1) | 2.1 (2.0-3.2) | 3.7 (2.1-4.2) |
| 36-month rate, % (95% CI) | 5.4 (2.1-11.0) | 2.3 (0.2-10.5) | NA |
| OSa | |||
| Median (95% CI), mo | 9.5 (6.4-11.9) | 7.9 (5.9-10.2) | 14.1 (10.8-17.6) |
| 36-month rate, % (95% CI) | 9.8 (5.5-15.5) | 9.0 (3.6-17.2) | 7.0 (2.3-15.6) |
aBy KM method. + indicates ongoing response.
Clinical trial identification
NCT02787005, June 1, 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.S. Antonarakis: Financial Interests, Personal, Advisory Role: Amgen, Astellas, AstraZeneca, Bayer, Clovis Oncology, Dendreon, Eli Lilly, ESSA, GlaxoSmithKline, Janssen, Medivation, Merck, Sanofi; Financial Interests, Personal, Funding: AstraZeneca, Bristol Myers-Squibb, Celgene, Clovis Oncology, Dendreon, Genentech, Janssen, Johnson & Johnson, Merck, Novartis, Sanofi, Tokai; Financial Interests, Personal, Royalties: Qiagen. J.M. Piulats: Financial Interests, Personal, Advisory Role: MSD, Janssen, BMS, Roche, Astellas, Bayer, BeiGene, VCN, Immunocore; Financial Interests, Personal, Research Grant: MSD, Janssen, BeiGene, Novartis. M. Gross-Goupil: Financial Interests, Personal, Other, Honoraria: Astellas, MSD, Janssen, Ipsen, BMS, Amgen, Bayer, AstraZeneca, Sanofi; Financial Interests, Personal, Advisory Role: Astellas, MSD, Janssen, Ipsen, BMS, Amgen, Bayer, AstraZeneca, Sanofi; Financial Interests, Personal, Other, Travel Expenses: Astellas, MSD, Janssen, Ipsen, BMS, Amgen, Bayer, AstraZeneca, Sanofi. J.C. Goh: Financial Interests, Personal, Advisory Role: MSD, GSK, BMS; Financial Interests, Personal, Speaker’s Bureau, Expert Testimony: MSD, GSK, AstraZeneca, BMS, Ipsen; Financial Interests, Personal, Other, Travel Expenses: AstraZeneca. U.N. Vaishampayan: Financial Interests, Personal, Other, Honoraria: AAA, Alkermes, Bayer, Pfizer, BMS, Exelixis; Financial Interests, Personal, Advisory Role: Merck, BMS, Exelixis; Financial Interests, Institutional, Research Grant: Merck, BMS. R. De Wit: Financial Interests, Personal, Other, Honoraria: Merck, Sanofi, Bayer, Astellas; Financial Interests, Personal, Advisory Role: Merck, Sanofi, Bayer, Astellas; Financial Interests, Institutional, Research Grant: Bayer. T.V. Alanko: Financial Interests, Personal, Advisory Role: Baxalta/Shire, BMS, Celgene, MSD, Nordic Drugs, Roche, Servier, Pfizer; Financial Interests, Institutional, Research Grant: AbbVie, Bayer, Boehringer Ingelheim, BMS, Eli Lilly, Incyte, MSD, Pfizer, Roche, Debiopharm, GlaxoSmithKline, TILT Biotherapeutics; Financial Interests, Personal, Other, Travel Expenses: Baxalta/Shire, BMS, MSD, Pfizer, Roche, Servier. K. Tabata: Financial Interests, Personal, Speaker’s Bureau, Expert Testimony: Janssen. S. Feyerabend: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Bayer and Aventis; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Travel Expenses: Aventis. K. Ojamaa: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche; Financial Interests, Personal, Advisory Role: AstraZeneca. C.J. Hoimes: Financial Interests, Personal, Advisory Role: Merck, Seagen, BMS, Genentech, Bayer; Financial Interests, Personal, Speaker’s Bureau: Seagen, BMS, Genentech, Eisai. A.G. Omlin: Financial Interests, Institutional, Other, Honoraria: AstraZeneca, Astellas, Bayer, BMS, Janssen, Molecular Partners, MSD, Pfizer, Roche, Sanofi Aventis; Financial Interests, Institutional, Research Grant: TEVA, Janssen; Financial Interests, Personal, Other, Travel Expenses: Astellas, Bayer, Janssen, Sanofi Aventis. C. Niu: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel Expenses: Merck Sharp & Dohme. C.H. Poehlein: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck; Financial Interests, Personal and Institutional, Leadership Role: Merck; Financial Interests, Personal and Institutional, Stocks/Shares: Merck. C. Schloss: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck. J.S. de Bono: 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; Financial Interests, Personal, Proprietary Information: Self. All other authors have declared no conflicts of interest.