Study Design and Patient Population

EP: 1.Introducing KEYNOTE-B61 in Non–Clear Cell RCC

EP: 2.Challenges in Treating Non–Clear Cell RCC

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EP: 3.Study Design and Patient Population

EP: 4.Representativeness of Histologies in Clinical Practice

Study Design and Patient Population

The KEYNOTE-B61 study represents the largest prospective clinical trial evaluating pembrolizumab plus lenvatinib as first-line treatment for advanced non–clear cell RCC, with nearly 160 patients enrolled. This single-arm phase 2 study builds upon the established efficacy of this combination in clear cell RCC, extending its application to the challenging non–clear cell population. Previous analysis with a median follow-up of 22.8 months demonstrated promising results with a 51% response rate and median progression-free survival of 17.9 months, though overall survival data remained immature at that time point.

The study design enrolled 158 treated patients with stage IV non–clear cell RCC who received lenvatinib 20 mg daily plus pembrolizumab 400 mg every 6 weeks for up to 18 cycles. The primary end point was overall response rate, with the current analysis providing updated data with extensive follow-up of 41.6 months minimum, representing more than 3 years of patient observation. This extended follow-up period allows for a more mature assessment of the durability of responses and long-term outcomes in this patient population.

A particularly noteworthy strength of the KEYNOTE-B61 study is its comprehensive inclusion of the major non–clear cell RCC histologic subtypes that clinicians encounter in practice. The study enrolled patients with papillary, chromophobe, unclassified, and translocation RCC, providing a representative sample of the heterogeneous non–clear cell population. This inclusive approach contrasts with other studies, such as trials with cabozantinib and nivolumab, which excluded certain subtypes such as chromophobe RCC after observing limited activity in early patients. The broad histologic representation enhances the clinical applicability of the study results across the spectrum of patients with non–clear cell RCC seen in routine clinical practice.