First-line pembrolizumab plus lenvatinib for non–clear cell renal carcinomas (nccRCC): Extended follow-up of the phase 2 KEYNOTE-B61 study.

Author(s): Martin H Voss1; Howard Gurney2; Vagif Atduev3; Cristina Suárez4; Miguel Ángel Climent5; David William Pook6; Piotr Tomczak7; Philippe Barthelemy8; Jae-Lyun Lee9; Taron Nalbandian10; Viktor Stus11; Thomas Ferguson12; Pawel Wiechno13; Erhan Gokmen14; Louis Lacombe15; Craig Gedye16; Joseph E. Burgents17; Manish Sharma17; Jerry Cornell17; Laurence Albiges18
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Data supports using this as first line therapy showing durable antitumor activity and manageable toxicity, thankfully not common tumors.


Pembrolizumab (pembro) + lenvatinib (lenva) is approved for first-line treatment of advanced/metastatic RCC based on results of the phase 3 KEYNOTE-581/CLEAR study. Previously reported results from the phase 2 KEYNOTE-B61 (NCT04704219) study with a median follow-up of 15 months further support the use of pembro + lenva in the first-line setting specifically across nccRCC. We now report updated results from KEYNOTE-B61 with median follow-up of 23 months.


Adults with previously untreated, advanced nccRCC (histology assessed by investigator) and measurable disease per RECIST v1.1 received pembro 400 mg IV Q6W for ≤18 cycles (~2 years) + lenva 20 mg orally once daily until intolerable toxicity, progressive disease, or patient (pt) withdrawal from the study. Primary end point was ORR per RECIST v1.1 by blinded independent central review (BICR). Secondary end points included DCR, DOR, and PFS per RECIST v1.1 by BICR, OS, and safety.


A total of 158 pts received pembro + lenva. Median age was 60 years (range, 24-87), and the most common histologic variants of RCC were papillary (n = 93; 59%), chromophobe (n = 29; 18%), and unclassified (n = 20; 13%). Median time from first dose to the data cutoff date of July 5, 2023, was 22.8 months (range, 16.6-27.6). 86 pts had discontinued treatment (most commonly due to progressive disease, n = 56 [35%]). In all pts, ORR was 51% (95% CI, 43-59; 13 CRs [8%]; 67 PRs [42%]) and DCR was 82% (95% CI, 75-88). Median DOR was 19.5 months (range, 15.3-not reached [NR]). An estimated 51% of responses had a duration of ≥18 months. ORR and DCR by histology are shown in the table. In all pts, median PFS and OS were 17.9 months (95% CI, 15.1-22.1) and NR (95% CI, NR-NR); estimated 18-month PFS and OS rates were 48% and 73%. Treatment-related AEs (TRAEs) occurred in 151 pts (96%), most commonly hypertension (56%), diarrhea (46%), hypothyroidism (41%), and proteinuria (30%). Grade 3-4 TRAEs occurred in 92 pts (58%), most commonly hypertension (25%), and diarrhea, proteinuria, and decreased weight (5% each). No deaths due to TRAEs were reported. Discontinuation due to TRAEs for pembro, lenva, or both pembro and lenva occurred in 15%, 13% and 4% of pts, respectively.


Consistent with prior reports, pembro + lenva had durable antitumor activity and a manageable safety profile in pts with advanced nccRCC. These results continue to support pembro + lenva as a first-line treatment option for pts with variant histologies of nccRCC.

Author Affiliations

1Memorial Sloan Kettering Cancer Center, New York, NY; 2Macquarie University, Sydney, NSW, Australia; 3Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russian Federation; 4Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 5Instituto Valenciano de Oncología, Valencia, Spain; 6Monash Health, Melbourne, VIC, Australia; 7Poznan University of Medical Sciences, Poznan, Poland; 8Institut de cancérologie Strasbourg Europe (ICANS), Strasbourg, France; 9Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; 10Regional Cancer Center, Kharkiv, Kharkiv, Ukraine; 11Dnipro State Medical University, Dnipro, Ukraine; 12Fiona Stanley Hospital, Perth, Western Australia, Australia; 13Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland; 14Ege University Medical Faculty, Izmir, Turkey; 15Centre de Recherche du CHU de Québec, Québec, QC, Canada; 16University of Newcastle, Callaghan, Australia; 17Merck & Co., Inc., Rahway, NJ; 18Gustave Roussy, Université Paris Saclay, Paris, France

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