Abstract 666P
Background
In the open-label, single-arm, phase II KEYNOTE-427 study (NCT02853344), first-line pembro monotherapy showed antitumor activity in pts with advanced ccRCC (cohort A). Updated efficacy and safety results after a minimum of 40.9 mo of follow-up for pts with ccRCC are presented.
Methods
Pts with histologically confirmed ccRCC 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. The primary end point was ORR per RECIST v1.1 by blinded independent review (BICR). Secondary end points included DOR and PFS per RECIST v1.1 by BICR, OS, and safety.
Results
Of 110 enrolled pts, 42 (38.2%) pts had favorable IMDC risk and 68 (61.8%) had intermediate/poor risk. As of February 5, 2021, median duration of therapy was 8.5 mo (range, 0.03-26.7). Median time from enrollment to data cutoff date was 47.3 mo (range, 40.9-51.7). ORR was 36.4% (95% CI, 27.4-46.1; 4 [3.6%] CR, 36 [32.7%] PR). Median DOR was 18.9 mo (95% CI, 7.1-37.7); an estimated 43.5% of responders remained in response for ≥24 mo. Overall, 69.0% had a reduction in in the sum of target lesions; 19.1% had a ≥80% reduction in the sum of target lesions. By IMDC risk category, ORR was 31.0% (95% CI, 17.6-47.1) in pts with favorable risk and 39.7% (95% CI, 28.0-52.3%) in pts with intermediate/poor risk. For all pts, median PFS was 7.1 mo (95% CI, 5.6-11.0) and median OS was 40.7 mo (95 CI, 31.1 to not reached); 30-mo PFS and OS rates were 19.9% and 62.6%, respectively. In pts with favorable risk, median PFS was 9.7 mo (95% CI, 5.6-12.4) and median OS was not reached (95% CI, 40.1 to not reached); PFS and OS rates at 30 mo were 16.4% and 78.3%, respectively. In pts with intermediate/poor risk, median PFS was 6.9 mo (95% CI, 3.3-11.0) and median OS was 30.8 mo (95% CI, 23.8-47.1); PFS and OS rates at 30 mo were 22.4% and 52.9%, respectively. No new safety signals were observed.
Conclusions
After a minimum of 40.9 mo, pembro monotherapy was well tolerated, and it continued to show promising antitumor activity as first-line treatment in advanced ccRCC, with no new safety signals.
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
D.F. McDermott: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Alkermes; Financial Interests, Personal, Advisory Board: Iovance; Financial Interests, Personal, Advisory Board: werewolf therapeutics; Financial Interests, Personal, Advisory Board: Calithera; Financial Interests, Institutional, Invited Speaker: BMS. J. Lee: Financial Interests, Personal, Other, Honoraria: Novartis Korea, AstraZeneca; Financial Interests, Personal, Advisory Role: Pfizer Korea, Ipsen Korea, Sanofi Aventis, Astella Korea, BMS, MSD, Merck, Esai, AstraZeneca; Financial Interests, Institutional, Stocks/Shares: Merck, Amgen, Johnson and Johnson, Myovant Science; Financial Interests, Personal, Stocks/Shares: Pfizer, Ipsen, BMS, MSD, Merck, Esai, Roche, AstraZeneca, Exelixis, Seagen. 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. J. Larkin: Financial Interests, Personal, Other, Honoraria: Roche, Novartis, iOnctura, BMS, Pfizer, Incyte, Dynavax, CRUK, GSK, Eisai, Merck, touchIME, touchExperts; Financial Interests, Personal, Advisory Role: Iovance, Boston Biomedical, Pfizer, BMS, GSK, Novartis, Incyte, Immunocore, YKT Global, iOnctura, Apple Tree; Financial Interests, Institutional, Research Grant: BMS, MSD, Novartis, Pfizer, Achilles, Roche, Nektar, Covance, Immunocore, Pharmacyclics, Aveo; Financial Interests, Personal, Other, Travel Expenses: BMS, Pfizer, Incyte, Roche, Pierre Fabre, AstraZeneca, Novartis, EUSA Pharma, MSD, 3Ervaxx, Merck, GSK, Ipsen, Aptitude, Eisai, Calithera, Ultimovacs, Seagen. R. Gafanov: Financial Interests, Institutional, Other, Honoraria: Janssen,MSD, Bayer, AstraZeneca; Financial Interests, Personal, Advisory Role: 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, Astra Zenec; Financial Interests, Institutional, Funding: Janssen,MSD, Bayer, AstraZeneca. F. Donskov: Financial Interests, Institutional, Funding: Ipsen, Pfizer, MSD. A. Poprach: Financial Interests, Personal, Other, Honoraria: BMS, Merck , MSD, Novartis, Pfizer, Bayer-Schering, and Roche; Financial Interests, Personal, Other, Travel Expenses: BMS, Roche. S.S. Tykodi: Financial Interests, Personal, Advisory Role: Merck, Intellisphere LLC, Natera, Bristol-Myers Squibb, Exelixis; Financial Interests, Personal, Funding: Genentech, Bristol-Myers Squibb, Merck, Calithera Biosciences, Pfizer, Jounce Therapeutics, Nektar, Exelixis, Clinigen Group. T. Alonso-Gordoa: Financial Interests, Personal, Invited Speaker, Advisory Role: IPSEN, Pfizer, Roche, Sanofi, Bayer, Astellas, Janssen-Cilag, MSD, BMS, EISAI; Financial Interests, Personal, Advisory Role: Roche, Sanofi, Bayer, Astellas, Janssen-Cilag, MSD. D.C. Cho: Financial Interests, Personal, Advisory Role: Pfizer, Nektar, Werewolf, HUYA. P.F. Geertsen: Financial Interests, Personal, Other, Honoraria: Roche, MSD, Pfizer, BMS; Financial Interests, Institutional, Research Grant: Roche. M.A. Climent Duran: Financial Interests, Personal, Other, Honoraria: BMS, Astellas, Janssen, MSD, Sanofi, Bayer, Roche, Pfizer, Novartis, Ipsen; Financial Interests, Personal, Advisory Role: BMS, MSD, Bayer, EUNSA, Pfizer, Roche, Janssen, Pierre Fabre, Ipsen; Financial Interests, Personal, Other, Travel Expenses: Janssen, Astellas, Roche, Ipsen, MSD. H. Liu: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. J. Burgents: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. K. Rodriguez-Lopez: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. M.B. Atkins: Financial Interests, Personal, Advisory Role: 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, AstraZenecam Calithera; Non-Financial Interests, Personal, Other: SITC, MRF, MRA, NIH. All other authors have declared no conflicts of interest.