Abstract 625P
Background
Pembo + enza (cohort C) has shown antitumor activity and acceptable safety in abi-pretreated patients (pts) with mCRPC in the phase I/II KEYNOTE-365 study (NCT02861573). Updated results from cohort C including time to symptomatic skeletal event, radiographic bone progression, and radiographic soft tissue progression are reported.
Methods
Pts who failed or became intolerant to abi after ≥4 wks of treatment in the prechemotherapy mCRPC state and who progressed within 6 mo of screening received pembro 200 mg IV Q3W + enza 160 mg/day orally. Primary end points: PSA response rate (decrease ≥50% from baseline, confirmed by a second value ≥3 wks later), ORR per RECIST v1.1 by blinded independent central review (BICR), and safety. Secondary end points: DCR, DOR; rPFS per PCWG-modified RECIST; OS, time to symptomatic skeletal event, radiographic bone progression, and radiographic soft tissue progression.
Results
102 of 103 enrolled pts were treated; 39% had measurable disease. Median (range) time from enrollment to data cutoff was 19.1 mo (1.1-28.8) for all pts and 21.4 mo (15.1-28.8) for pts with ≥27 wks’ follow-up (n=69). Confirmed PSA response rate was 22% in 101 pts with a baseline PSA assessment. In pts with measurable disease and ≥27 wks’ follow-up (n=25), confirmed ORR was 12% (2 CRs, 1 PR). For all pts, median rPFS was 6.1 mo (95% CI, 4.4-6.5) and median OS was 20.4 mo (95% CI, 15.5-NR). At 12 mo, rPFS rate was 24.6% and OS rate was 72.8% by Kaplan-Meier. Additional efficacy analyses are displayed in the table. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 40 pts (39%); 3 pts died of AEs (1 TRAE [cause unknown]).
Conclusions
Pembro + enza continued to show activity in pts with abi-pretreated mCRPC. Safety of the combination was consistent with the known profiles of pembro and enza. The phase III KEYNOTE-641 study of this combination is ongoing (NCT03834493). Table: 625P
| DCR, n/N (%)a | |
| Measurable disease | 8/25 (32) |
| Nonmeasureable disease | 16/44 (36) |
| Total | 24/69 (35) |
| Median (range) DOR, moa | NR (0.0+-24.4+)b |
| Median (95% CI), mo | |
| Time to confirmed PSA progression | 3.5 (2.9-4.0) |
| Time to symptomatic skeletal-related event | NR (18.2-NR) |
| Event-free survival rate at 12 mo, % | 75.5 |
| Time to radiographic bone progression | 8.3 (6.7-10.8) |
| Event-free survival rate at 12 mo, % | 32.9 |
| Time to radiographic soft-tissue progression | 15.2 (6.7-NR) |
| Event-free survival rate at 12 mo, % | 56.8 |
aWith ≥27 wks’ follow-up;b ‘+’ indicates ongoing responder;NR, not reached.
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
L. Mourey: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: MSD. H.J. Conter: Full/Part-time employment: Hoffmann-La Roche Canada; Advisory/Consultancy: Janssen; Advisory/Consultancy: Roche; Travel/Accommodation/Expenses: Bayer. N. Shore: Leadership role, Immediate past president: LUGPA; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Dendreon; Advisory/Consultancy, Travel/Accommodation/Expenses: Ferring; Advisory/Consultancy, Travel/Accommodation/Expenses: Fergene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: MDxHealth; Advisory/Consultancy, Travel/Accommodation/Expenses: Myovant; Advisory/Consultancy, Travel/Accommodation/Expenses: Nymox; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi-Genzyme; Advisory/Consultancy, Travel/Accommodation/Expenses: Tolmar. W.R. Berry: Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy: Genomic Health; Research grant/Funding (self): Merck. 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, Speaker Bureau/Expert testimony: 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. L.J. Appleman: Research grant/Funding (institution): Acerta; Research grant/Funding (institution): Agensys; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Aveo; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Calithera; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Inovio; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Peloton; Research grant/Funding (institution): Tokai. 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): 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. H. Gurney: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Roche. E. Romano: Research grant/Funding (institution): BMS; Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Merck/MSD; Travel/Accommodation/Expenses: Roche. 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. U. Emmenegger: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Astellas. H. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. P. Qiu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. C. Schloss: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. 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: 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: 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): Taiho. All other authors have declared no conflicts of interest.