Abstract 2091
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.
Resources from the same session
4868 - Evaluation of markers associated with efficacy of abiraterone acetate plus prednisone (AAP) in patients (pts) with castration-sensitive prostate cancer (mCSPC) from the LATITUDE study
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
4837 - LRP2, a potential new biomarker for Chinese younger aged intrahepatic cholangiocarcinoma patients
Presenter: Xiaoliang Shi
Session: Poster Display session 3
Resources:
Abstract
1286 - Reanalysis of the efficacy of molecular targeted agents (MTAs) given in the randomized trial SHIVA01 according to the ESMO ESCAT scale of actionability
Presenter: Aurelie Moreira
Session: Poster Display session 3
Resources:
Abstract
2736 - Comparison of Platforms for Determining Tumor Mutational Burden (TMB) From Blood Samples in Patients With Non-Small Cell Lung Cancer (NSCLC)
Presenter: Jonathan Baden
Session: Poster Display session 3
Resources:
Abstract
5045 - Comprehensive Pan-Cancer analysis of somatic mutations in drug transporters to reveal acquired and intrinsic drug resistance in 3149 metastatic cancer patients
Presenter: Sander Bins
Session: Poster Display session 3
Resources:
Abstract
4577 - Pan-Cancer Genomic Landscape of the Cyclin D1/FGF3,4,19 (11q13) Amplicon Including Associations with HPV Status, and ESR1 and AR Alterations
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
5366 - Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients
Presenter: Xiaolong Jiao
Session: Poster Display session 3
Resources:
Abstract
4084 - Prospective comparative study of next-generation sequencing on fine needle aspirations versus core needle biopsies in cancer patients included in SHIVA02 trial
Presenter: Julien Masliah-Planchon
Session: Poster Display session 3
Resources:
Abstract
6017 - First national External Quality Assessement for the interpretation of somatic variants: assessment of 25 variants in colorectal, lung, ovarian cancers and melanoma in France
Presenter: Etienne Rouleau
Session: Poster Display session 3
Resources:
Abstract
2283 - Prospective testing of circulating tumor DNA in metastatic breast cancer facilitates clinical trial enrollment and precision oncology
Presenter: Andjelija Bujak
Session: Poster Display session 3
Resources:
Abstract