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
4596 - A Phase 2, Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-Mutant Melanoma Brain Metastasis (MBM) (POLARIS)
Presenter: Michael Davies
Session: Poster Display session 3
Resources:
Abstract
1891 - Continuation of annual screening mammograms and breast-cancer mortality in women over 70
Presenter: Xabier Garcia De Albeniz
Session: Poster Display session 3
Resources:
Abstract
5587 - Introducing standardized medical procedure and dynamic decision support program in precision oncology for the community of practice
Presenter: Istvan Petak
Session: Poster Display session 3
Resources:
Abstract
4757 - Effectively using primary care givers in oncology care through capacity building, task sharing and techno-mentoring.
Presenter: Dinesh Pendharkar
Session: Poster Display session 3
Resources:
Abstract
4497 - A single institution review of capecitabine related acute admissions and cost analysis
Presenter: Gemma Dart
Session: Poster Display session 3
Resources:
Abstract
2187 - Health status of middle-aged and older cancer survivors in China: results from the China Health and Retirement Longitudinal Study (CHARLS)
Presenter: Jiarui Li
Session: Poster Display session 3
Resources:
Abstract
5101 - Crossed looks on lung cancer perception and knowledge from general public and physicians in France: results of a two-fold survey
Presenter: Céline Mascaux
Session: Poster Display session 3
Resources:
Abstract
4354 - Knowledge and perception of clinical trials (CTs) and attitude towards participation among Polish oncological patients - A pilot survey
Presenter: Artur Kotowski
Session: Poster Display session 3
Resources:
Abstract
3499 - Achieving best possible cancer treatment outcomes in care pathways through benchmarking; ABC-Benchmarking
Presenter: Anke Wind
Session: Poster Display session 3
Resources:
Abstract
2270 - Impact of 10-day Fulbright Specialist Program (FSP) and Project Pink Blue (PPB) Education Sessions on Medical Oncology knowledge among Doctors that treat cancer in Nigeria
Presenter: Mike Martin
Session: Poster Display session 3
Resources:
Abstract