2091 - First-Line Pembrolizumab (pembro) Monotherapy in Advanced Clear Cell Renal Cell Carcinoma (ccRCC): Updated Follow-Up For KEYNOTE-427 Cohort A

Background

KEYNOTE-427 (NCT02853344) is an open-label, single-arm, phase 2 study to evaluate efficacy and safety of first-line single-agent pembro in patients (pts) with ccRCC (cohort A) and non–ccRCC (cohort B). Updated follow-up data from cohort A are presented.

Methods

Pts with histologically confirmed ccRCC, measurable per RECIST v1.1, and no prior systemic therapy were eligible. Pts received pembro 200 mg IV Q3W for 2 y or until confirmed progressive disease, unacceptable toxicity, or pt decision to withdraw. Primary end point: objective response rate (ORR; RECIST v1.1 by blinded independent central review). Additional end points: duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results

110 pts enrolled; median (range) follow-up was 22.6 (2.5-27.5) mo. Median age was 64 (29-87) y; 38.2%, 47.3%, and 14.5% of pts had favorable, intermediate, and poor IMDC risk, respectively; 47.3% of tumors were PD-L1 positive. Confirmed ORR was 36.4% (95% CI, 27.4-46.1; 3 [2.7%] CR, 37 [33.6%] PR) and median (range) DOR was not reached (2.3 - 23.5+ mo). For responding pts, 64.0% had a response ≥12 mo (Kaplan-Meier estimates). Median PFS was 7.1 mo (95% CI, 5.6-11.0) and median OS was not reached; 12 mo PFS and OS rates were 37.6% and 88.2%, respectively. By IMDC, confirmed ORR was 39.7% for immediate/poor risk and 31.0% for favorable risk. For responding pts, 80.9% and 69.2% of immediate/poor and favorable risk, respectively had a response ≥6 mo; 65.5% and 61.5%, respectively, had a response ≥12 mo. For sarcomatoid differentiated tumors (n = 11), confirmed ORR was 63.6%; 71.4% had a response of ≥ 12 mo. By PD-L1 status, confirmed ORR was 44.2% and 29.3% for positive and negative, respectively. Treatment-related AEs occurred in 81.8%, with fatigue (29.1%) and pruritus (28.2%) the most common. One pt died of treatment-related pneumonitis.

Conclusions

With a median of 23-mo follow-up, first-line pembro monotherapy continued to show promising efficacy in pts with advanced ccRCC. Safety profile was comparable to previously reported.

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

Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

J.M.G. Larkin: Honoraria (self): Achilles, AZ, Boston Biomedical, BMS, Eisai, EUSA Pharma, GSK, Ipsen, Imugene, Incyte, iOnctura, Kymab, Merck Serono, MSD, Nektar, Novartis, Pierre Fabre, Pfizer, Roche / Genentech, Secarna, Vitaccess; Advisory / Consultancy: Achilles, AZ, Boston Biomedical, BMS, Eisai, EUSA Pharma, GSK, Ipsen, Imugene, Incyte, iOnctura, Kymab, Merck Serono, MSD, Nektar, Novartis, Pierre Fabre, Pfizer, Roche / Genentech, Secarna, Vitaccess; Travel / Accommodation / Expenses: Achilles, AZ, Boston Biomedical, BMS, Eisai, EUSA Pharma, GSK, Ipsen, Imugene, Incyte, iOnctura, Kymab, Merck Serono, MSD, Nektar, Novartis, Pierre Fabre, Pfizer, Roche / Genentech, Secarna, Vitaccess; Research grant / Funding (institution): BMS, MSD, Novartis, Pfizer, Achilles Therapeutics, Roche, Nektar Therapeutics, Covance, Immunocore, Pharmacyclics, Aveo. S.S. Tykodi: Advisory / Consultancy, Research grant / Funding (institution): Calithera Biosciences; Advisory / Consultancy, Research grant / Funding (institution): Prometheus Laboratories; Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Peloton Therapeutics; Research grant / Funding (institution): Nektar Therapeutics; Research grant / Funding (institution): Jounce Therapeutics; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): ARGOS Therapeutics. F. Donskov: Honoraria (institution): Pfizer; Honoraria (institution): Ipsen. J. Malik: Advisory / Consultancy: Eisai; Travel / Accommodation / Expenses: Eusa. 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. 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. P.F. Geertsen: Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Pfizer. 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. 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), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Progenics. T. Alonso Gordoa: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (self): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Novartis. 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), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Honoraria (self), Advisory / Consultancy: Array BioPharm; Honoraria (self), Advisory / Consultancy: Genentech BioOncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Alkermes; Honoraria (self), Advisory / Consultancy: Jounce Therapeutics; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): X4 Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Peloton Therapeutics; Honoraria (self), Advisory / Consultancy: EMD Serono; Honoraria (self), Advisory / Consultancy: Eli Lilly; Research grant / Funding (institution): Prometheus Laboratories; Research grant / Funding (institution): Genentech. M.B. Atkins: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Eisai; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Array. All other authors have declared no conflicts of interest.