4712 - First-Line Pembrolizumab (pembro) Monotherapy for Advanced Non‒Clear Cell Renal Cell Carcinoma (nccRCC): Updated Follow-Up for KEYNOTE-427 Cohort B

Background

KEYNOTE-427 (NCT02853344) is a single-arm, open-label, phase 2 study of pembro monotherapy in patients (pts) with advanced clear cell RCC (cohort A) and nccRCC (cohort B). Updated cohort B results with additional follow-up are presented.

Methods

165 pts with histologically confirmed nccRCC, no prior systemic therapy, and measurable disease (RECIST v1.1) enrolled. Pts received pembro 200 mg IV Q3W for 35 cycles (∼2 y) or until progressive disease, unacceptable toxicity, or withdrawal. Primary end point: objective response rate (ORR, RECIST v1.1 by blinded independent central review). Additional end points: duration of response (DOR), PFS, OS, data by sarcomatoid differentiation, histology, and PD-L1 expression (combined positive score [CPS] ≥1 for PD-L1+).

Results

Histology by central pathology review: papillary 72% (n = 118), chromophobe 13% (n = 21), unclassified 16% (n = 26); 62% were PD-L1+. Median follow-up: 15.0 mo (range, 0.9-25.4). Overall ORR was 26.1% (95% CI, 19.5-33.5; 10 [6.1%] CR, 33 [20.0%] PR) and median (range) DOR was 15.3 mo (2.8-21.0+). For responders, 57.3% had a response ≥12 mo. 12-mo PFS and OS rates were 24.7% and 73.7%, respectively. ORR (95% CI) was 28.0% (20.1-37.0) in papillary, 9.5% (1.2-30.4) in chromophobe, and 30.8% (14.3-51.8) in unclassified nccRCC; for responders, 55.4%, 50.0%, and 71.4% in the papillary, chromophobe and unclassified groups had a response ≥12 mo. Median (range) DOR was not reached in the unclassified and was 15.3 mo (2.8-21.0+) for the papillary group. ORR (95% CI) was 42.1% (26.3-59.2) for pts with sarcomatoid differentiation (n = 38). ORR (95% CI) in pts with CPS≥1 and CPS<1 was 35.3% (26.1-45.4) and 10.3% (3.9-21.2), respectively. Grade 3-5 treatment-related adverse events (TRAEs) occurred in 14% of pts. 7 pts died of AEs, 2 of TRAEs (pneumonia and cardiac arrest).

Conclusions

Single-agent pembro continued to show encouraging antitumor activity in nccRCC, especially with papillary or unclassified histology and CPS≥1. Safety profile of pembro was as expected.

Clinical trial identification

NCT02853344, August 2, 2016.

Editorial acknowledgement

Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA), 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

C. Suárez: Advisory / Consultancy: Astellas, BMS, Eusa, Ipsen, Novartis, Pfizer, Sanofi-Aventis; Research grant / Funding (self): Ipsen; Speaker Bureau / Expert testimony: AstraZeneca, BMS, Ipsen, Pfizer; Travel / Accommodation / Expenses: Roche, Pfizer, Ipsen; Research grant / Funding (institution): AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, INC, Astellas Pharma., AstraZeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim España, S.A., Bristol-Myers Squibb Intern; Non-remunerated activity/ies: Roche Steering Committee. J. Lee: Honoraria (self): Novartis Korea, BMS Korea; Advisory / Consultancy: Pfizer Korea, Janssen, Sanofi Aventis, Astellas Korea, BMS Korea, Ipsen Korea; Leadership role: Korea Cancer Study Group. M. Ziobro: Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Novartis. V.B. Matveev: Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Astellas. F. Donskov: Honoraria (institution): Pfizer; Honoraria (institution): Ipsen. F. Pouliot: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Progenics. B.Y. Alekseev: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Ferring; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi. P.J. Wiechno: Honoraria (self): Bayer; Honoraria (self): BMS; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Astellas; Honoraria (self): Ipsen; Honoraria (self): Janssen-Cilag; Honoraria (self): Novartis. M.A. Climent: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Pfizer. R. Kloss Silverman: Full / Part-time employment: Merck & Co., Inc. R.F. Perini: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. C. Schloss: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. D.F. McDermott: Honoraria (self), Research grant / Funding (self): BMS; Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self), Research grant / Funding (self): Merck; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): Exelixis; Honoraria (self): Array BioPharm; Honoraria (self), Research grant / Funding (self): Genentech BioOncology; Honoraria (self), Research grant / Funding (self): Alkermes, Inc.; Honoraria (self): Jounce Therapeutics; Honoraria (self), Research grant / Funding (self): X4 Pharma; Honoraria (self), Research grant / Funding (self): Peloton Therapeutics; Honoraria (self): EMD Serono; Honoraria (self): Eli Lilly and Company; Research grant / Funding (self): Prometheus Laboratories. M.B. Atkins: Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Genentech/Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Eisai; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Array; Advisory / Consultancy, Research grant / Funding (self): BMS. All other authors have declared no conflicts of interest.