Abstract 621P
Background
Pembro + olaparib has shown antitumor activity and acceptable safety in docetaxel-pretreated pts with mCRPC enrolled in cohort A of the phase I/2 KEYNOTE-365 study (NCT02861573). Updated results including time to symptomatic skeletal event, radiographic bone progression, and radiographic soft tissue progression are reported.
Methods
Pts with docetaxel-pretreated mCRPC with disease progression within 6 mo of screening received pembro 200 mg IV Q3W + olaparib 400-mg capsule or 300-mg tablet orally twice daily. Pts could have received 1 other chemotherapy and ≤2 second-generation androgen receptor–targeted therapies. Primary end points: PSA response rate (decrease ≥50% from baseline), ORR per RECIST v1.1 by blinded independent central review, and safety. Secondary end points: DCR, composite response rate, DOR, rPFS per PCWG-modified RECIST, OS, time to symptomatic skeletal event, radiographic bone progression, and radiographic soft tissue progression.
Results
84 of 87 enrolled pts were treated; 48 of 84 (57.1%) had measurable disease. Median (range) time from enrollment to data cutoff was 3.6 (0.0-29.2) mo for all pts and 26.7 (21.2-29.2) mo for 41 pts with ≥27 wk follow-up. Confirmed PSA response rate in 82 pts with PSA at baseline was 9%. Confirmed ORR in pts with measurable disease and ≥27 wk potential follow-up (n = 24) was 8% (2 PRs). Median rPFS was 4.3 mo (95% CI, 3.4-7.7) and median OS was 14.4 mo (95% CI, 8.1-18.5). At 12 mo, rPFS rate was 23.3% and OS rate was 58.2% by Kaplan-Meier. Additional analyses are displayed in the table. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 29 pts (35%); 2 pts died of TRAEs (1 myocardial infarction, 1 unknown). Table: 621P
| DCR, n/N (%)a Measurable disease Nonmeasurable disease Total | 5/24 (21) 4/17 (24) 9/41 (22) |
| DOR, median (range), moa | NR (12.0+-21.4+)b |
| Composite response rate, n/N (%) | 8/84 (10) |
| Median (95% CI), mo | |
| Time to confirmed PSA progression | 3.7 (2.8-4.4) |
| Time to symptomatic skeletal-related event | NR (13.8-NR) |
| Event-free survival rate at 12 mo, % | 77.6 |
| Time to radiographic bone progression | 6.5 (4.1-16.1) |
| Event-free survival rate at 12 mo, % | 28.8 |
| Time to radiographic soft tissue progression | 21.7 (5.9-NR) |
| Event-free survival rate at 12 mo, % | 54.2 |
NR, not reached.aWith ≥27 wk potential follow-up.b ‘+’ indicates ongoing responder.
Conclusions
Pembro + olaparib continued to show activity and acceptable safety in pts with docetaxel-pretreated mCRPC. A phase III study of this combination is ongoing (KEYLYNK-010, NCT03834519).
Clinical trial identification
NCT02861573.
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
J.A. Arranz Arija: Advisory/Consultancy: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: EUSA; Travel/Accommodation/Expenses: Ipsen; Research grant/Funding (institution): BMS (SOGUG). E.Y. Yu: Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Advanced Accelerator Applications; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Clovis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Dendreon; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pharmacyclics; Honoraria (self), Advisory/Consultancy: QED; Honoraria (self), Advisory/Consultancy: Sanofi-Genzyme; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Honoraria (self), Advisory/Consultancy: Tolmar; Research grant/Funding (institution): Daiichi-Sankyo; Research grant/Funding (institution): Taiho. J.M. Piulats: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy: Bayer; Advisory/Consultancy: Sanofi-Genzyme; Advisory/Consultancy, Research grant/Funding (self): MSD; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (self): Merck-Serono; Advisory/Consultancy: Clovis; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): BeiGene; Advisory/Consultancy, Research grant/Funding (self): VCN Biotech. G. Gravis: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (institution), Travel/Accommodation/Expenses: MSD; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Travel/Accommodation/Expenses: Astellas; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (institution), Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen. B. Laguerre: Honoraria (self): BMS; Honoraria (self), Travel/Accommodation/Expenses: Astellas; Honoraria (self), Travel/Accommodation/Expenses: Janssen; Honoraria (self): AstraZeneca; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Novartis. S. Oudard: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi. P.C. Fong: Advisory/Consultancy: MSD, Pfizer; Travel/Accommodation/Expenses: Pfizer. M.P. Kolinsky: Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self): Astellas; Honoraria (self): Bayer; Advisory/Consultancy: Ipsen; Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck; Travel/Accommodation/Expenses: Novartis. M. Augustin: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: PharmaMar; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): MorphoSys. H. Gurney: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Roche. W.R. Berry: Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy: Genomic Health; Research grant/Funding (self): Merck. P. Qiu: 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 Biosyhstems, Daiichi Sankyo, Sierra Oncology, Bayer, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim, Celgene, Taiho Pharmaceuticals, Genmab, GlaxoSm; Non-remunerated activity/ies, Preclinical Studies: AstraZeneca, Genentech, Sanofi, Taiho Pharmaceuticals, Daiichi Sankyo, erck Serono, Astex Pharmaceuticals, Merck Sharp & Dohme, Orion Pharma, GlaxoSmithKline, CellCentric, Celgene, Sierra Oncology, Bayer, Medimmume, Medivation, Terumo, Astellas Pharma, Ge. All other authors have declared no conflicts of interest.