Abstract 623P
Background
We present results including time to cytotoxic chemotherapy and time to new anticancer therapy from the multicohort phase 2 study KEYNOTE-199 (NCT02787005) in chemotherapy-naive patients (pts) with mCRPC treated with pembrolizumab (pembro) + enzalutamide (enza) after progression on enza and who had RECIST-measurable (C4) or bone-predominant nonmeasurable (C5) disease.
Methods
Pts with or without prior abiraterone were eligible if they developed resistance to enza following prior response. Pts continued on enza and received pembro 200 mg IV Q3W for up to 2 y or until progression, toxicity, or withdrawal. End points: ORR per RECIST v1.1 (C4) by blinded independent central review (primary), DOR (C4), DCR, rPFS per PCWG3-modified RECIST, OS, time to cytotoxic chemotherapy, time to new anticancer therapy, and safety.
Results
126 pts (C4, 81; C5, 45) were treated. Median (range) PSA was 31 ng/mL (0.4-1667) in C4 and 19 ng/mL (1-1750) in C5. Median (range) time from enrollment to data cut off was 15 mo (7-21) in C4 and 19 mo (7-21) in C5. 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. Efficacy analyses are displayed in the table. Grade ≥3 treatment-related AEs occurred in 26% of pts in C4 and 24% in C5. Two pts in C4 died of immune-related AEs (Miller Fisher syndrome and myasthenia gravis). Incidence of any grade/grade 3-4 rash (regardless of treatment relatedness) was higher than previously reported for individual agents (33%/6%) but manageable with standard of care treatments. Table: 623P
| Cohort 4 | Cohort 5 | |
| ORR, by RECIST v1.1, n/N (%) | 10/81 (12) | NA |
| DCR, n/N (%) | 41/81 (51) | 23/45 (51) |
| PSA response rate in patients with baseline PSA, n/N (%) | 13/80 (16) | 4/45 (9) |
| Time to PSA progression | ||
| Median (95% CI),a mo | 4.2 (4.1-4.4) | 4.2 (4.2-4.4) |
| rPFS | ||
| Median (95% CI),a mo | 4.2 (2.5-6.0) | 4.4 (3.4-6.2) |
| rPFS rate at 12 mo, % | 17 | 23 |
| OS | ||
| Median (95% CI),a mo | NR (15.9-NR) | 18.8 (14.0-NR) |
| OS rate at 12 mo, % | 70 | 75 |
| Time to cytotoxic chemotherapy | ||
| Median (95% CI),a mo | 11.1 (8.5-NR) | 11.3 (9.0-14.5) |
| Event-free survival rate at 12 mo, % | 47 | 48 |
| Time to new anticancer therapy | ||
| Median (95% CI),a mo | 9.4 (7.2-11.1) | 9.5 (5.9-12.1) |
| Event-free survival rate at 12 mo, % | 38 | 35 |
aProduct-limit (Kaplan-Meier) method for censored data.
Conclusions
Pembro + enza after enza resistance had manageable safety and showed antitumor activity for RECIST-measurable and bone-predominant mCRPC. This combination is being evaluated in the ongoing KEYNOTE-641 phase III trial (NCT03834493).
Clinical trial identification
NCT02787005.
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.G. Omlin: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy: MSD; Advisory/Consultancy: Molecular Partners; Research grant/Funding (institution): Teva. J.N. Graff: Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy: Astellas; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Valeant; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Travel/Accommodation/Expenses: Clovis. C.J. Hoimes: Honoraria (institution): 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; Non-remunerated activity/ies: Atlab Pharma, Telix Pharma, Phosplatin Therapeutics. R. McDermott: Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers-Squibb; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Array Biopharma; Advisory/Consultancy, Research grant/Funding (institution): Peloton Therapeutics; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Alkermes; Advisory/Consultancy: Lilly; Advisory/Consultancy: Eisai; Research grant/Funding (institution): Prometheus Laboratories; Non-remunerated activity/ies, other: BIDMC; Non-remunerated activity/ies: X4 Pharmaceuticals; Non-remunerated activity/ies: AVEO; Research grant/Funding (institution): Genentech. U.N. Vaishampayan: Advisory/Consultancy, Research grant/Funding (institution): Merck & Co., Inc.. T. Elliott: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen. W.R. Gerritsen: Advisory/Consultancy: BMS; Advisory/Consultancy: IqVia; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Janssen-Cilag; Research grant/Funding (institution): Astellas. H. Wu: Full/Part-time employment: Merck & Co., Inc.. 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, Advisory board: AstraZeneca, Sanofi, Astellas Pharma, Pfizer, Genentech/Roche, Janssen Oncology, Menarini Silicon Biosystems, Daiichi Sankyo, Sierra Oncology, Bayer, MSD, Merck Serono, Boehringer Ingelheim, Celgene, Taiho Pharmaceuticals, Genmab, GlaxoSmithKline, Orion P; Research grant/Funding (institution): AstraZeneca, Genentech, Sanofi, Taiho Pharmaceuticals, Daiichi Sankyo, Merck Serono, Astex Pharmaceuticals, MSD, Orion, GlaxoSmithKline, Cellcentric, Cellgene, Sierra Oncology, Bayer, Medimmune, Medivation, Terumo, Astellas Pharma, Genmab, Janssen. E.S. Antonarakis: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Janssen; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Sanofi; Honoraria (self), Advisory/Consultancy: Dendreon; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Medivation; Honoraria (self), Advisory/Consultancy: ESSA; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Clovis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck; Research grant/Funding (self): Johnson & Johnson; Research grant/Funding (self): Genentech; Research grant/Funding (self): Novartis; Research grant/Funding (self): Bristol Myers-Squibb; Honoraria (self), Advisory/Consultancy: Eli Lilly; Research grant/Funding (self): Tokai; Research grant/Funding (self): Celgene; Honoraria (self), Advisory/Consultancy: Amgen; Licensing/Royalties, Patent holder/licenser; licenser of technology: Qiagen; Advisory/Consultancy: Bayer; Advisory/Consultancy: GlaxoSmithKline. All other authors have declared no conflicts of interest.