Updated results from the phase 2 LITESPARK-003 trial with belzutifan and cabozantinib have been published in the Lancet Oncology. The study showed that the combination of belzutifan and cabozantinib had promising anti-cancer activity with manageable side effects in patients with advanced clear cell kidney cancer who had not previously been treated.

In total, 50 patients with untreated advanced clear cell kidney cancer were enrolled in the study. After 24 months of follow-up, 7 in 10 patients (70%) responded to treatment with 4 patients (8%) having a complete response and all signs of their cancer disappeared.  6 in 10 patients (62%) had a partial response and their cancer shrank. More than a quarter of patients (28%) had stable disease, and the cancer got worse (progressed) in only 1 patient. The average duration of response was over two years (28.6 months).

The disease was controlled in the majority of patients (49 of 50 patients, 98%). Estimated overall survival rates were 96% of patients at 12 months and 86% at 24 months.

All patients reported at least one side effect, of which nearly half were serious or life-threatening and related to treatment. The most common serious or life-threatening treatment-related side effects included high blood pressure, low red blood cell count (anaemia), fatigue, low oxygen levels, and hand-foot syndrome.

Overall, about half of the patients stopped treatment, primarily due to progression of disease.

“To our knowledge, this is the first trial in a first-line setting to show that the VEGFR-targeting combination of an HIF-2α inhibitor and tyrosine kinase inhibitor has manageable toxicity,” the researchers wrote. “Our findings provide rationale for further randomised trials of belzutifan in combination with other tyrosine kinase inhibitor-based regimens.”

The LITESPARK-003 trial remains ongoing, with final completion anticipated in February 2027.

Read more in Urology Times here