LITESPARK-011 Signals Shifting Paradigm in RCC

Data presented at the Genitourinary Cancers Symposium may soon reshape the treatment landscape for patients with renal cell carcinoma across multiple disease stages, according to Dr. Yousef Zakharia, a medical oncologist specializing in genitourinary malignancies who serves as chair for the genitourinary malignancy program at the Mayo Clinic enterprise and leads experimental therapeutics at Mayo Clinic Arizona.

Dr. Zakharia highlighted the LITESPARK-011 trial, which examined patients with metastatic clear cell renal cell carcinoma who had progressed on a checkpoint inhibitor. In this randomized study of approximately 700 patients, those who progressed on PD-1 inhibition received either belzutifan, a HIF-2 alpha inhibitor dosed at 120 milligrams daily, in combination with lenvatinib at 20 milligrams daily, versus cabozantinib at 60 milligrams daily. The trial met its primary end point of improving progression-free survival in favor of the belzutifan and lenvatinib combination, with results showing 14.8 months versus 10.7 months for cabozantinib, representing a hazard ratio of 0.70.

Particularly impressive was the duration of response data. At two years, 49% of patients on the belzutifan and lenvatinib arm continued responding to treatment, compared with 25% of those on cabozantinib. "This speaks to the fact maybe belzutifan applied earlier on in the course of the disease stage might be helping with that tail of the curve," Dr. Zakharia said. "I do anticipate this combination will become FDA approved and will be a practice-changing regimen. Matter of fact, I already had two of my patients asking for this regimen after reading about it online, after the results were released at GU ASCO."

The field now awaits results from LITESPARK-012, which examines the same combination in treatment-naïve patients with metastatic clear cell renal cell carcinoma. This three-arm study randomized patients to triple therapy with pembrolizumab, lenvatinib, and belzutifan versus pembrolizumab and lenvatinib alone versus pembrolizumab, lenvatinib, and a CTLA-4 inhibitor. Results are expected later this year.