KEY TAKEAWAYS
- The phase 2 study named KEYNOTE-B61 trial, aimed to evaluate the combination of pembro + lenva as a first-line treatment. It confirmed the objective response rate per RECIST v1.1 by BICR.
- The study enrolled adult patients with detectable disease per RECIST v1.1, and they received pembro 400 mg IV Q6W up to 18 cycles (2 y) + lenva 20 mg orally QD.
- Patients who were followed up for at least 24 weeks had a confirmed ORR of 47.6% (95% CI, 36.4-58.9), with 3 CRs (3.7%) and 36 PRs (43.9%).
- The most common treatment-related AEs were hypertension, diarrhea, and hypothyroidism (n=37; 25.2%
- The combination of pembro and lenva encouraged antitumor activity with tolerable side effects in patients with advanced nccRCC.
Compared to sunitinib, the combination of pembro + lenva in first-line treatment of ccRCC enhanced overall survival, progression-free survival, and objective response rate (ORR) in phase 3 KEYNOTE-581 research. Cohort B of phase 2 KEYNOTE-427 study of pembro monotherapy as first-line treatment for nccRCC demonstrated encouraging antitumor activity. Here researchers present interim findings from KEYNOTE-B61, a single-arm, phase 2 research (NCT04704219) designed to assess the efficacy of pembro + lenva as frontline therapy for nccRCC. Pembro 400 mg IV Q6W up to 18 cycles (2 y) + lenva 20 mg orally QD was given to adults with advanced, untreated nccRCC and detectable disease per RECIST v1.1. Confirmed ORR (CR + PR) per RECIST v1.1 by BICR was the primary endpoint, with progression-free survival (PFS), overall survival (OS), and safety as supplementary endpoints. Patients treated and followed up with for at least 24 weeks were considered adequate. All treated patients were assessed for safety.
Papillary, chromophobe, and unclassified histologies accounted for 87 (50.2%), 26 (17.7%), and 19 (12.9%) of the 147 patients that were treated; translocation (4.1%), medullary (0.7%), and other (5.4%) histologies accounted for 15 (5.4%) patients. For patients eligible for a follow-up period of 24 weeks (n=82) as of January 31, 2022, the median follow-up was 8.2 months (range 5.5-10.5). The 82 patients had a confirmed ORR of 47.6% (95% CI, 36.4-58.9), with 3 CRs (3.7%) and 36 PRs (43.9%). There was a DCR of 79.3% (95% CI = 68.9-87.4). There was no determined median DOR (1.4+ to 7.2+ months). The table displays ORR and DCR by histologic subgroup. Overall survival (OS) at 6 months was 87.8% (95% CI, 78.5-93.2), and progression-free survival (PFS) at 6 months was 72.3% (95% CI, 60.7-81.0).
There were 127 patients (86.4%) who experienced some form of treatment-related adverse event (AE), with hypertension (n=71; 48.3%), diarrhea (n=37; 25.2%), and hypothyroidism (n=37; 25.2%) being the most common. TRAEs of grades 3-4 occurred in 51 percent of cases (34.7%). TRAEs caused no fatalities. Patients with advanced nccRCC responded well to the combination of pembro and lenva, and side effects were tolerable. There were no additional warning signs that appeared with this mixture.
Source:https://oncologypro.esmo.org/meeting-resources/esmo-congress/phase-ii-keynote-b61-study-of-pembrolizumab-pembro-lenvatinib-lenva-as-first-line-treatment-for-non-clear-cell-renal-cell-carcinoma-nccrcc
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04704219/
L. Albiges, H.P. Gurney, V. Atduev, C. Suárez, M.A. Climent Duran, D. Pook, P. Tomczak, P. Barthelemy, J. Lee, T. Nalbandian, V. Stus, T. Ferguson, P. Wiechno, E. Gokmen, L. Lacombe, C. Gedye, R.F. Perini, M. Sharma, C. Li, C. Lee/Phase II KEYNOTE-B61 study of pembrolizumab (Pembro) + lenvatinib (Lenva) as first-line treatment for non-clear cell renal cell carcinoma (nccRCC)/Annals of Oncology (2022) 33 (suppl_7): S660-S680. 10.1016/annonc/annonc1072
