KEYNOTE-B61 Investigates Pembrolizumab Plus Lenvatinib in RCC

Chung-Han Lee, MD, PhD, a medical oncologist specializing in genitourinary malignancies at Memorial Sloan Kettering Cancer Center, discusses the phase 2 KEYNOTE-B61 trial (NCT04704219) of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) in patients with non–clear cell renal cell carcinoma (RCC).

After this combination was investigated in patients with metastatic clear cell RCC in the phase 3 KEYNOTE-581/CLEAR trial (NCT02811861), researchers thought this promising combination might work for those with non–clear cell RCC. The KEYNOTE-B61 trial is currently accruing patients to test the combination of immunotherapy plus a tyrosine kinase inhibitor (TKI).

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0:08 | Right now, there is a lot of interest in looking at novel combinations of immune checkpoint inhibitors and TKIs for non–clear cell RCC. This type of combination has been studied fairly extensively for clear cell RCC, where we have multiple FDA-approved regimens, and also multiple regimens that have gained National Comprehensive Cancer Network designation. These have included combinations such as axitinib [Inlyta] plus pembrolizumab, cabozantinib [Cabometyx] plus nivolumab [Opdivo], axitinib plus avelumab [Bavencio], and lenvatinib plus pembrolizumab.

0:48 | The idea behind looking at this within non–clear cell RCC is that, historically speaking, non–clear cell RCC has been much more resistant to systemic therapies; however, it can still benefit from treatment with regimens that were approved and designed for clear cell RCC. The idea behind KEYNOTE-B61 is examining the combination of lenvatinib plus pembrolizumab and gain a further understanding of whether or not there would be additional benefit this type of regimen within the non–clear cell space.

1:32 | This is a single-arm, phase 2 study of 152 patients treated with the combination of lenvatinib, at 20 mg daily, and pembrolizumab, at 400 mg every 6 weeks. The primary end point of the study was looking at the objective response rate by RECIST v1.1, and key secondary end points included clinical benefit rate, disease control rate, duration of response, progression-free survival, overall survival, and safety. Perhaps the most interesting of this, beyond just looking at those standard efficacy end points, is also several exploratory end points were built in looking at biomarker analysis to better understand which cohorts may benefit from this combination.

2:25 | This is a trial that is currently ongoing, and we are just starting the process of accruing patients as the trials in progress. This is currently accruing in North America, Europe, Asia, and Australia. It is probably too early to speak about any of the results from the trial, but we are encouraged by the results that we have seen in clear cell space, [where] we saw high objective response rates and also a very long duration of response. Other trials looking at the combination [of] lenvatinib include the investigator-initiated trial of lenvatinib plus everolimus [Afinitor], which also showed promising efficacy results. So we look forward to seeing what this type of combination will do.