Abstract 662P
Background
In the single-arm, open-label, phase II KEYNOTE-427 study, first-line pembro monotherapy showed antitumor activity in nccRCC (cohort B) (NCT02853344). We present updated efficacy and safety results after a minimum of 34.1 mo of follow-up for pts with nccRCC.
Methods
Pts with histologically confirmed nccRCC and measurable disease per RECIST v1.1 who had not previously received systemic therapy were given pembro 200 mg IV every 3 weeks for up to 35 doses or until progressive disease, unacceptable toxicity, or withdrawal of consent. Primary end point was ORR per RECIST v.1.1 by blinded independent central review (BICR). Secondary end points were DOR and PFS per RECIST v1.1 by BICR, OS, and safety.
Results
Of 165 pts, 118 (71.5%) had papillary histology, 21 (12.7%) had chromophobe histology, and 26 (15.8%) were unclassified. As of February 5, 2021, median duration of therapy was 6.9 mo (range, 0.03-29.2); 55 (33.3%) pts received ≥12 mo of treatment and 25 (15.2%) completed pembro treatment (35 doses). Median time from enrollment to data cutoff date was 42.9 mo (range, 34.1-50.2). ORR was 26.7% (95% CI, 20.1-34.1; 11 CRs, 33 PRs). Median DOR was 29.0 mo (95% CI, 9.8-not reached); an estimated 53.8% of responders remained in response for at least 24 mo. Median PFS was 4.2 mo (95% CI, 2.9-5.6) and median OS was 29.9 mo (95% CI, 24.3-37.4). At 30 mo, the PFS rate was 16.9% and the OS rate was 48.4%. Most pts (59.4%) had a reduction in the sum of target lesions; 16.4% had a ≥80% reduction in the sum of target lesions. ORR (95% CI) was 28.8% (95% CI, 20.8-37.9), 9.5% (95% CI, 1.2-30.4), and 30.8% (95% CI, 14.3-51.8) for pts with papillary, chromophobe, and unclassified histology, respectively. Treatment-related AEs occurred in 114 (69.1%) of pts and grade 3-5 treatment-related AEs occurred in 28 (17.0%) pts. Two pts died of treatment-related AEs (pneumonia and cardiac arrest).
Conclusions
After a minimum of 34.1 mo of follow-up, pembro monotherapy continued to demonstrate promising antitumor activity as first-line treatment in advanced nccRCC. No new safety signals were observed.
Clinical trial identification
NCT02853344, August 2, 2016.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD of ApotheCom (Yardley, PA, USA). This assistance was 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
J. Lee: Financial Interests, Personal, Other, Honoraria: Novartis Korea, AstraZeneca; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Pfizer Korea, Ipsen Korea, Sanofi Aventis, Astella Korea, BMS, MSD, Merck, Esai, AstraZeneca; Financial Interests, Personal, Stocks/Shares: Merck, Amgen, Johnson and Johnson, Myovant Science; Financial Interests, Institutional, Research Grant: Pfizer, Ipsen, BMS, MSD, Merck, Esai, Roche, AstraZeneca, Exelixis, Seagen. D.F. McDermott: Financial Interests, Personal, Other, Honoraria: BMS, Pfizer, Merck, Alkermes, Inc., EMD, Serono, Eli Lilly and Company, Iovance, Eisai Inc. Werewolf Therapeutics, Calithera Biosciences; Financial Interests, Personal, Research Grant: BMS, Merck, Genentech, Pfizer, Exelixis, X4 Pharma, Alkermes, Inc., Checkmate Pharmaceuticals. M. Ziobro: Financial Interests, Personal, Other, Honoraria: BMS, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: BMS, MSD, Pierre-Fabre; Financial Interests, Personal, Speaker’s Bureau, Speaker Bureau/Expert Testimony: BMS, MSD; Financial Interests, Personal, Other, Travel expenses, including accommodations: BMS, MSD, Novartis, Pfizer, Roche. C. Suarez: Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb, Ipsen, Sanofi, Pfizer, EUSA Pharma, Astellas Pharma, Novartis, Merck Sharp & Dohme Speakers’ Bureau: Bristol-Myers Squibb, Ipsen, PfizerRoche/Genentech, AstraZeneca, Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Astellas Pharma, Roche/Genentech, Exelixis, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Janssen Oncology, Calithera Biosciences, AB Science, Arog, AVEO, Bayer, SFJ Pharmaceuticals Group, Blueprint Medicines, Clovis Oncology, Boehringer Ingelheim,; Financial Interests, Personal, Other, Travel Expenses: Bristol-Myers Squibb, Roche, Ipsen. P. Langiewicz: Financial Interests, Personal, Research Grant: Merck, Astellas. V.B. Matveev: Financial Interests, Personal, Other, Honoraria: Bayer, Janssen, AstraZeneca, Astellas, BMS, Merk, Roche; Financial Interests, Personal, Advisory Role: Eisai. P. Wiechno: Financial Interests, Personal, Invited Speaker, Honoraria: Pfitzer, Astellas, Janssen Cilag, Bayer, MSD, BMS; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Pfitzer, Astellas, Janssen Cilag, Bayer, MSD, BMS. R. Gafanov: Financial Interests, Institutional, Other, Honoraria: Janssen, MSD, Bayer, AstraZeneca; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Astellas, Janssen,Sanofi, Pfizer, BMS, MSD, Bayer, Eisai, Ipsen, Pierre Fabre, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau, Speaker Bureau/Expert Testimony: Astellas, Janssen,Sanofi, Pfizer, BMS, MSD, Bayer, Eisai, Ipsen, Pierre Fabre, AstraZeneca; Financial Interests, Personal, Leadership Role: Astellas, Janssen,Sanofi, Pfizer, BMS, MSD, Bayer, Eisai, Ipsen, Pierre Fabre, AstraZeneca; Financial Interests, Institutional, Research Grant: Janssen,MSD, Bayer, AstraZeneca. F. Pouliot: Financial Interests, Personal, Other, Honoraria: Tersera, Janssen, Astellas, Bayer, Sanofi, Ferring; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Tersera, Janssen, Astellas, Bayer, Sanofi, Ferring, Merck; Financial Interests, Personal, Speaker’s Bureau, Speaker Bureau/Expert Testimony: Janssen; Financial Interests, Personal, Other, Travel expenses, including accommodations: Amgen; Financial Interests, Institutional, Research Grant: Astellas, Bayer. F. Donskov: Financial Interests, Personal, Research Grant: Ipsen, Pfizer, MSD. B.Y. Alekseev: Financial Interests, Personal, Other, Honoraria: Astellas, AstraZeneca, Bayer, BMS, Eisai, Ferring, Ipsen, Janssen, Merck, MSD, Pfizer, Roche, Sanofi; Financial Interests, Institutional, Other, Honoraria: Astellas, AstraZeneca, Bayer, BMS, Eisai, Ferring, Ipsen, Janssen, Merck, MSD, Pfizer, Roche; Financial Interests, Personal, Advisory Role: Astellas, AstraZeneca, Bayer, BMS, Eisai, Ipsen, Janssen, Merck, MSD, Pfizer, Roche; Financial Interests, Personal, Speaker’s Bureau: Astellas, AstraZeneca, Bayer, BMS, Eisai, Ferring, Ipsen, Janssen, Merck, MSD, Pfizer, Roche, Sanofi; Financial Interests, Personal, Funding: Astellas, AstraZeneca, Bayer, BMS, Eisai, Ferring, Ipsen, Janssen, Merck, MSD, Pfizer, Roche, Sanofi; Financial Interests, Personal, Other, Travel Expenses: Astellas, AstraZeneca, Bayer, BMS, Eisai, Ferring, Ipsen, Janssen, Merck, MSD, Pfizer, Roche; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Bayer, BMS, Eisai, Ferring, Ipsen, Janssen, Merck, MSD, Pfizer, Roche. G.A. Bjarnason: Financial Interests, Personal, Other, Honoraria: Pfizer, BMS, Eisai, Ipsen, Merck; Financial Interests, Personal, Advisory Role: Pfizer, BMS, Eisai, Ipsen, Merck; Financial Interests, Personal, Research Grant: Pfizer. Merck. D. Castellano: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, BMS, GSK, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche; Non-Financial Interests, Institutional, Principal Investigator: Astellas, AstraZeneca, Bayer, BMS, Clovis, Eisai, Exelisis, GSK, Ipsen, Janssen, Lilly, MSD, Pfizer, QED Therapeutics, Roche; Non-Financial Interests, Personal, Member, Executive member: SOGUG (Spanish Oncology Genito-Urinary Group). H. Liu: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. J. Burgents: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. K. Rodriguez-Lopez: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. M.B. Atkins: Financial Interests, Personal, Advisory Role, Advisory/consultancy: BMS, Merck, Novartis, Arrowhead, Eisai, Aveo, Pfizer, Werewolf, Fathom, Pneuma, Leads, Pyxis Oncology, PACT, Elpis, X4Pharma, ValoHealth, ScholarRock, Surface, Genentech-Roche, Exelixis, ImmunoCore, Iovance, Idera, Agenus, Apexigen, Asher Bio, Neoleukin; Financial Interests, Personal, Stocks/Shares: Werewolf, Pyxis Oncology, Elpis; Financial Interests, Institutional, Research Grant: BMS, Merck, DOD, NIH, AstraZeneca, Calithera; Financial Interests, Personal, Other, Non-remunerated activity/ies: SITC, MRF, MRA, NIH. All other authors have declared no conflicts of interest.