Dr McDermott on the Eligibility Criteria of the LITESPARK-024 Trial in RCC

David F. McDermott, MD, director, the Biologic Therapy and Cutaneous Oncology Programs, Beth Israel Deaconess Medical Center, professor, medicine, Harvard Medical School, discusses the ongoing, randomized, phase 1/2 LITESPARK-024 trial (NCT05468697) in patients with advanced renal cell carcinoma (RCC), highlighting the eligibility criteria for this clinical trial.

This open-label study is evaluating the use of belzutifan (Welireg), a HIF2α inhibitor, in combination with palbociclib (Ibrance), a CDK4/6 inhibitor, compared with belzutifan monotherapy in patients with advanced RCC. Notably, in August, 2021, the FDA approved treatment with belzutifan for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated RCC.

This phase 1/2 LITESPARK-024 trial aims to identify the phase 2 study dose, McDermott begins, adding that patients are required to have been exposed to VEGF blockade and PD-1 blockade and are therefore asecond- or third-line study population. Otherwise, this trial has standard eligibility criteria for patients, including presentation of metastatic clear cell kidney cancer, a good Karnofsky performance status, and normal lab values, he adds.

Notably, the HIF2α-inhibiting class of drugs has a novel and somewhat narrow safety profile, McDermott expands. These drugs can cause fatigue, which is often related to anemia, though this can be reversed with erythropoietin injections, McDermott adds. This class of drugs can also cause hypoxia, which can sometimes lead to treatment interruptions, he explains.

However, overall, HIF2α inhibitors are generally better tolerated than other agents for patients with kidney cancer, McDermott continues. HIF2α inhibitors have a narrower spectrum of toxicities than the VEGF inhibitors, for example, making these drugs good candidates for combination approaches, he emphasizes. CDK4/6 inhibitors are associated with a broader list of adverse effects that can affect the bone marrow or the gastrointestinal tract, the latter of which can lead to diarrhea, he highlights. The LITESPARK-024investigators need to understand the possibility for overlapping toxicities between belzutifan and palbociclib, he concludes.