Dr McGregor on the Investigation of Abemaciclib Monotherapy in ccRCC

Bradley McGregor, MD, director, Clinical Research, Lank Center of Genitourinary Oncology, Dana-Farber Cancer Institute; instructor, medicine, Harvard Medical School, discusses the rationale for investigating abemaciclib (Verzenio) monotherapy in patients with clear cell renal cell carcinoma (ccRCC).

At the 2024 Kidney Cancer Research Summit, investigators presented findings from a phase 1b study (NCT04627064) evaluating the CDK4/6 inhibitor as a monotherapy in patients with ccRCC. Although the safety profile of the agent was tolerable, none of the patients who received abemaciclib (n = 11) achieved a response; 8 patients had disease progression and 1 patient had stable disease.

There has been significant interest in developing new therapeutic targets for RCC, particularly exploring the synergy between CDK4/6 inhibitors and HIF2α inhibitors, McGregor begins. Preclinical data indicate that CDK4/6 inhibition may enhance the effects of HIF2α inhibition; however, clinical data on CDK4/6 inhibitors as monotherapy in ccRCC have been lacking, he explains. To address this gap, a phase 1 trial assessed the role of the CDK4/6 inhibitor in combination with the HIF2α inhibitor belzutifan (Welireg) for ccRCC treatment, McGregor notes. Before advancing to the combination phase of this trial, investigators recognized the need for data on the effectiveness of CDK4/6 inhibitors as standalone agents in this disease, he states. Therefore, the trial’s initial design included 2 separate arms examining abemaciclib both as monotherapy and in combination with belzutifan. Due to various factors, the arm investigating the combination of abemaciclib with belzutifan was closed, McGregor reports.

A total of 11 patients with heavily pretreated ccRCC were enrolled in the monotherapy arm, he continues. These patients were treated with abemaciclib until they experienced unacceptable toxicity or disease progression. Although the combination approach did not move forward, the data from the single-agent arm provides valuable insights into the potential role of CDK4/6 inhibition in treating patients with ccRCC, McGregor concludes.