Pembrolizumab/lenvatinib labels updated to include KEYNOTE-B61 data in non-ccRCC

The US labels for pembrolizumab (Keytruda) and lenvatinib (Lenvima) have been updated to include clinical efficacy data from the phase 2 KEYNOTE-B61 trial of the combination in patients with non-clear cell renal cell carcinoma (non-ccRCC).¹

The combination led to an objective response rate of 51%.

The combination of pembrolizumab (an anti-PD-1 therapy) and lenvatinib (a multiple receptor tyrosine kinase inhibitor)was approved in August 2021 for the first-line treatment of adult patients with advanced RCC.² Although the recent label update includes an addition of data in non-ccRCC, the approved indication for the combination remains unchanged.

With the addition of the new data, the combination of pemrolizumab and lenvatinib becomes the first and only combination for the first-line treatment of advanced RCC with labels that include data in both clear cell and non-clear cell RCC.

"Non-clear cell RCC is an aggressive, challenging-to-treat disease, and our goal is to address those unmet needs and advance care for these patients," said Takashi Owa, PhD, chief scientific officer and senior vice president of Eisai Co.Ltd, in a news release.¹ "The addition of efficacy data from the KEYNOTE-B61 trial reinforces the important role of KEYTRUDA plus LENVIMA as a frontline treatment option for adult patients with advanced RCC regardless of histology. We are proud to realize this development through our collaboration with Merck to improve the lives of more people affected by cancer, and we are grateful to the patients and investigators whose involvement made this advancement possible."

The labels were updated to reflect clinical efficacy data from the phase 2 KEYNOTE-B61 trial (NCT04704219), which evaluated the combination of pembrolizumab and lenvatinib in the frontline treatment of patients with advanced non-ccRCC.

In the trial, the combination led to an objective response rate (ORR) of 51% (95% CI, 43-59), which comprised a complete response rate of 8% and a partial response rate of 42%. The median duration of response (DOR) in the study was 19.5 months (range, 1.5+, 23.5+, with + indicating an ongoing response). A duration of 18 months or longer was estimated in 51% of patients.

Additional data presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium earlier this year reported a disease control rate (DCR) of 82% (95% CI, 75-88).³ The median progression-free survival (PFS) was 17.9 months (95% CI, 15.1-22.1), and the median overall survival (OS) had not yet been reached at the time of data report. The estimated 18-month PFS and OS rates were 48% and 73%, respectively.

No new safety signals were reported in the trial.

Overall, the single-arm, multicenter, phase 2 KEYNOTE-B61 trial enrolled 160 patients with previously untreated non-ccRCC. Of those, 158 patients received 20 mg oral lenvatinib once daily in combination with 400 mg pembrolizumab every 6 weeks for up to 24 months or until unacceptable toxicity or disease progression. Patients were able to receive lenvatinib monotherapy beyond 24 months until unacceptable toxicity or disease progression.

The median age of patients included in the trial was 60 years (range, 25-87 years). Of those included in the study, 86% were White, 8% were Asian, 3% were Black, and less than 1% were Hispanic or Latino. Further, IMDC risk category distributions were 35% favorable, 54% intermediate, and 10% poor.

The primary efficacy end point in the trial was ORR, as determined by blinded independent central review (BICR) per RECIST v1.1. Additional secondary efficacy measures included DOR per BICR using RECIST v1.1, as well as the DCR, PFS per BICR using RECIST v1.1, OS, and safety.

Final study completion is anticipated for October 2025.⁴

References

1. New efficacy data for non-clear cell renal cell carcinoma from KEYNOTE-B61 added to LENVIMA (lenvatinib) US label supporting KEYTRUDA + LENVIMA indication for the first-line treatment of adult patients with advanced RCC. News release. Eisai Inc. June 27, 2024. Accessed June 28, 2024. https://www.prnewswire.com/news-releases/new-efficacy-data-for-non-clear-cell-renal-cell-carcinoma-from-keynote-b61-added-to-lenvima-lenvatinib-us-label-supporting-keytruda--lenvima-indication-for-the-first-line-treatment-of-adult-patients-with-advanced-rcc-302185116.html

2. FDA approves lenvatinib plus pembrolizumab for advanced renal cell carcinoma. News release. US Food & Drug Administration. August 10, 2021. Accessed June 28, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lenvatinib-plus-pembrolizumab-advanced-renal-cell-carcinoma

3. Voss MH, Gurney H, Atduev V, et al. First-line pembrolizumab plus lenvatinib for non–clear cell renal carcinomas (nccRCC): Extended follow-up of the phase 2 KEYNOTE-B61 study. J Clin Oncol. 2024;42(suppl 4). doi:10.1200/JCO.2024.42.4_suppl

4. Pembrolizumab plus lenvatinib for first-line advanced/​metastatic non-clear cell renal cell carcinoma (1L nccRCC) (MK-3475-B61) (KEYNOTE-B61). ClinicalTrials.gov. Last updated January 2024. Accessed June 28, 2024. https://www.clinicaltrials.gov/study/NCT04704219