Belzutifan Plus Cabozantinib Shows Promise in Previously Treated Clear Cell Renal Cell Carcinoma

Among patients with clear cell renal cell carcinoma who have received previous PD-1/PD-L1 inhibition, belzutifan plus cabozantinib showed promising antitumor activity, according to a phase 2 study.

There is an unmet need for patients with advanced renal cell carcinoma who have received previous treatment with anti-PD-1- or anti-PD-L1-based immunotherapy. Lead investigator Toni Choueiri, MD, Dana-Farber Institute, Boston, MA, and coauthors wrote, “Combining belzutifan, an HIF-2α inhibitor, with cabozantinib, a multitargeted tyrosine-kinase inhibitor of VEGFR, c-MET, and AXL, might provide more antitumoral effects than either agent alone.”

In this phase 2 study, patients with locally advanced or metastatic clear cell renal cell carcinoma were enrolled into 2 cohorts between September 27, 2018 and July 14, 2020. Cohort 1 took patients with treatment naïve disease. In cohort 2 (n = 52), patients had previously received immunotherapy and up to 1 systemic treatment regiments. Patients were given 120 mg belzutifan once daily and 60 mg cabozantinib once daily. The primary end point of this study was confirmed objective response, as assessed by the investigator. Patients who received at least 1 dose of study treatment were included in the antitumor activity and safety assessment.

At the data-cutoff date of February 1, 2022 the median follow-up duration was 24.6 months. The confirmed objective response rate was 30.8% (n = 16), with 1 patient achieving a complete response and 15 partial responses. The most common grade 3/4 treatment-related adverse event was hypertension, occurring in 27% of patients. There were 15 patients who experienced serious treatment-related adverse events. There was 1 death that was determined to be treatment-related by the investigator, due to respiratory failure.

Dr Chouieri et al concluded, “Our findings provide rational for further randomised trials with belzutifan in combination with a VEGFR tyrosine-kinase inhibitor.

Source:

Choueiri TK, McDermott DF, Merchan J, et al. Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: An open-label, single-arm, phase 2 study. Lancet Oncol. Published online: March 31, 2023.