Abstract 4712
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.
Resources from the same session
5105 - Fresh blood Immune cell monitoring in patients treated with nivolumab in the GETUG-AFU26 NIVOREN study: association with toxicity and treatment outcome
Presenter: Aude DESNOYER
Session: Poster Display session 3
Resources:
Abstract
1877 - Advanced clear-cell renal cell carcinoma (accRCC): association of microRNAs (miRNAs) with molecular subtypes, mRNA targets and outcome.
Presenter: Annelies Verbiest
Session: Poster Display session 3
Resources:
Abstract
5543 - Prior tyrosine kinase inhibitors (TKI) and antibiotics (ATB) use are associated with distinct gut microbiota ‘guilds’ in renal cell carcinoma (RCC) patients
Presenter: Valerio Iebba
Session: Poster Display session 3
Resources:
Abstract
2689 - mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
Presenter: Cristina Suarez Rodriguez
Session: Poster Display session 3
Resources:
Abstract
3069 - Efficacy of immune checkpoint inhibitors (ICI) and genomic alterations by body mass index (BMI) in Advanced Renal Cell Carcinoma (RCC)
Presenter: Aly-Khan Lalani
Session: Poster Display session 3
Resources:
Abstract
5089 - Finding the Right Biomarker for Renal Cell Carcinoma (RCC): Nivolumab treatment induces the expression of specific peripheral lymphocyte microRNAs in patients with durable and complete response.
Presenter: Lorena Incorvaia
Session: Poster Display session 3
Resources:
Abstract
2594 - Algorithms derived from quantitative pathology can be a gatekeeper in patient selection for clinical trials in localised clear cell renal cell carcinoma (ccRCC)
Presenter: In Hwa Um
Session: Poster Display session 3
Resources:
Abstract
2566 - High baseline blood volume is an independent favorable prognostic factor for overall and progression-free survival in patients with metastatic renal cell carcinoma
Presenter: Aska Drljevic-nielsen
Session: Poster Display session 3
Resources:
Abstract
2675 - Impact of estimand selection on adjuvant treatment outcomes in renal cell carcinoma (RCC)
Presenter: Daniel George
Session: Poster Display session 3
Resources:
Abstract
1541 - TERT gene fusions characterize a subset of metastatic Leydig cell tumors
Presenter: Bozo Kruslin
Session: Poster Display session 3
Resources:
Abstract