Abstract 1448O
Background
In ccRCC, first-line pembro + lenva improved OS, PFS, and ORR vs sunitinib in the phase 3 KEYNOTE-581 study. In nccRCC, first-line pembro monotherapy showed promising antitumor activity in cohort B of the phase 2 KEYNOTE-427 study. We report the first results of KEYNOTE-B61, a single-arm, phase 2 study (NCT04704219) evaluating pembro + lenva as first-line treatment for nccRCC.
Methods
Adults with previously untreated advanced nccRCC and measurable disease per RECIST v1.1 received pembro 400 mg IV Q6W up to 18 cycles (∼2 y) + lenva 20 mg orally QD. Primary end point was confirmed ORR (CR + PR) per RECIST v1.1 by BICR; secondary end points were DOR, DCR (CR + PR + SD), PFS, OS, and safety. Efficacy was evaluated in treated pts who had the opportunity for ≥24 wk of follow-up. Safety was evaluated in all treated pts.
Results
Of 147 treated pts, 87 (59.2%), 26 (17.7%), and 19 (12.9%) had papillary, chromophobe, and unclassified histology, respectively; 15 pts had translocation (4.1%), medullary (0.7%), or other (5.4%) histology. As of January 31, 2022, median follow-up for pts who had the opportunity for ≥24 wk of follow-up (n=82) was 8.2 mo (range, 5.5-10.5). Of these 82 pts, confirmed ORR was 47.6% (95% CI, 36.4-58.9; 3 CRs [3.7%]; 36 PRs [43.9%]). DCR was 79.3% (95% CI, 68.9-87.4). Median DOR was not reached (range, 1.4+ to 7.2+ mo). ORR and DCR in histologic subgroups are shown in the table. The 6-month PFS rate was 72.3% (95% CI, 60.7-81.0) and the 6-month OS rate was 87.8% (95% CI, 78.5-93.2). In all treated pts (N=147), any grade treatment-related AEs (TRAEs) occurred in 127 pts (86.4%), most commonly hypertension (n=71; 48.3%), diarrhea (n=37; 25.2%), and hypothyroidism (n=37; 25.2%). Grade 3-4 TRAEs occurred in 51 pts (34.7%). No deaths occurred due to TRAEs. Table: 1448O
| Total N = 82 | Papillary n = 51 | Chromophobe n = 15 | Unclassified n = 7 | Translocation n = 5 | Other n = 4 | |
| ORR, % (95% CI) | 47.6 (36.4-58.9) | 52.9 (38.5-67.1) | 13.3 (1.7-40.5) | 71.4 (29.0-96.3) | 60.0 (14.7-94.7) | 50.0 (6.8-93.2) |
| DCR, % (95% CI) | 79.3 (68.9-87.4) | 78.4 (64.7-88.7) | 73.3 (44.9-92.2) | 100.0 (59.0-100.0) | 80.0 (28.4-99.5) | 75.0 (19.4-99.4) |
Conclusions
In this preliminary analysis, pembro + lenva showed promising antitumor activity and manageable safety in pts with advanced nccRCC. No new safety signals emerged with this combination.
Clinical trial identification
NCT04704219, Release date: January 11, 2021.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Robert Steger, PhD, and Mallory Campbell, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Eisai Inc., Nutley, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Eisai Inc., Nutley, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Eisai Inc., Nutley, NJ, USA.
Disclosure
L. Albiges: Financial Interests, Institutional, Other, Consulting: Astellas, AstraZeneca, BMS, EISAI, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer; Non-Financial Interests, Principal Investigator: Pfizer, BMS, Ipsen, AVEO, AstraZeneca, MSD; Non-Financial Interests, Other, Clinical trial steering committee: Roche, Exelixis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Other, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology (EAU); Non-Financial Interests, Other, Member of the Kidney Cancer Research Summit scientific committee 2021: Kidney Can; Other, Scientific Committee: BMS France. H.P. Gurney: Financial Interests, Personal, Advisory Board: Merck, Ipsen, Pfizer, MSD, Astellas, Parexel, BMS, AstraZeneca, Janssen, Eisai, Amgen. C. Suárez: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Ipsen, Pfizer, EUSA Pharma, Astellas Pharma, Merck Sharp & Dohme, Eisai; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Ipsen, Pfizer, Roche/Genentech, AstraZeneca, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb, Roche, Ipsen; 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, Cougar Biotechnology, Deciphera, GlaxoSmithKline, Incyte, Karyopharm Therapeutics, MedImmune, Nanobiotix, Millennium, Puma Biotechnology, Teva. M.A. Climent Duran: Financial Interests, Personal, Invited Speaker: BMS, MSD, Bayer, Pfizer, Merck, Astellas, Janssen, Ipsen, EUSA, Roche, Astra, Eisai; Financial Interests, Personal, Advisory Board: BMS, MSD, Bayer, Pfizer, Merck, Astellas, Janssen, Ipsen, EUSA, Roche, Astra, Eisai. D. Pook: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme. T. Ferguson: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Funding: Merck, Roche, BMS. E. Gokmen: Financial Interests, Personal, Invited Speaker: BMS, Roche, Pfizer, AstraZeneca, Novartis, Eli Lilly, Astellas, Janssen, Gilead, Amgen, Abdi Ibrahim, Mustafa Nevzat, Gen Ilac; Financial Interests, Personal, Advisory Board: BMS, Roche, Pfizer, AstraZeneca, Novartis, Eli Lilly, Astellas, Janssen, Gilead, Amgen, Abdi Ibrahim, Mustafa Nevzat, Gen Ilac. L. Lacombe: Non-Financial Interests, Institutional, Principal Investigator: CHU de Quebec-Université Laval. C. Gedye: Financial Interests, Institutional, Advisory Board: Merck EMD Serono, MSD, BMS, Astellas, Pfizer, AstraZeneca, Ipsen; Financial Interests, Institutional, Invited Speaker: Merck EMD Serono, MSD, BMS, Astellas, Pfizer, AstraZeneca, Ipsen; Financial Interests, Institutional, Other, Consulting: Merck EMD Serono, MSD, BMS, Astellas, Pfizer, AstraZeneca, Ipsen; Financial Interests, Institutional, Advisory Role: Limbic; Financial Interests, Institutional, Other, Travel support: BMS, Astellas, MSD; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Amgen, Merck Sharp & Dohme; Non-Financial Interests, Institutional, Other, Consulting: Novotech-CRO PTY; Non-Financial Interests, Institutional, Advisory Role: ANZUP Cancer Trials Group, COGNO, Mark Hughes Foundation, International Kidney Cancer Consortium. R. Perini: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. M. Sharma: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck, Regeneron. C. lI: Financial Interests, Personal, Full or part-time Employment: Merck. C. Lee: Financial Interests, Personal and Institutional, Advisory Board: BMS, Eisai, Exelixis, Merck, Pfizer; Financial Interests, Personal and Institutional, Principal Investigator: BMS, Eisai, Exelixis, Merck, Pfizer; Financial Interests, Institutional, Principal Investigator: Calithera, Eli Lilly; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Invited Speaker: AiCME, Intellisphere, Research to Practice. All other authors have declared no conflicts of interest.