Dr McGregor on Challenges and Future Research Directions in ccRCC

Bradley McGregor, MD, director, Clinical Research, Lank Center of Genitourinary Oncology, Dana-Farber Cancer Institute; instructor, medicine, Harvard Medical School, discusses the ongoing treatment challenges and future research directions with CDK4/6 inhibitiors in clear cell renal cell carcinoma (ccRCC).

At the 2024 Kidney Cancer Research Summit, McGregor presented findings from a phase 1b study (NCT04627064) evaluating the CDK 4/6 inhibitor abemaciclib (Verzenio) as monotherapy for patients with advanced pretreated ccRCC.

Of the 11 patients enrolled onto the study, 1 patient achieved a response, 8 patients experienced disease progression, and 1 patient experienced stable disease with abemaciclib. The agent also demonstrated a tolerable safety profile.

Although the study did not meet its primary end point, these findings could provide valuable insights into the feasibility of combining CDK4/6 inhibitors with other agents, which is being explored in several ongoing studies, McGregor notes. For example, the ongoing randomized phase 1/2 LITESPARK-024 study (NCT05468697) is comparing the combination of the CDK4/6 inhibitor palbociclib (Ibrance) with belzutifan (Welireg) vs belzutifan monotherapy in patients with metastatic ccRCC.

Despite the development of effective immunotherapy agents, such as nivolumab (Opdivo) and ipilimumab (Yervoy), as well as immune-oncology (IO) and TKI combinations, McGregor states that a significant proportion of patients do not achieve durable responses with these regimens and eventually require additional lines of therapy. This highlights the critical need for continued research to improve treatment outcomes, he adds.

One of the primary areas for future research in ccRCC, McGregor explains, is the identification of novel therapeutic targets that can enhance the efficacy of existing treatments or provide more avenues for intervention.

Although significant advancements have been made in the management of ccRCC, there remains a critical need for ongoing research to improve and expand therapeutic approaches in ccRCC, McGregor concludes.