Belzutifan cabozantinib combo shows durable anti-tumour effect at phase II for ccRCC

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Published: 22 Oct 2023
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Dr Toni Choueiri - Dana-Farber Cancer Institute, Boston, USA

Dr Choueiri talks to ecancer at ESMO 2023 about the phase II LITESPARK-003 study.

Results he presented indicated that the combination of belzutifan and cabozantinib represents a promising treatment for advanced clear cell renal cell carcinoma.

The study found the treatment option to be effective in both first-line and subsequent-line settings and showed durable anti-tumour activity with a safety profile consistent with prior observations.

These results further support the use of an HIF-2α inhibitor and VEGFR-TKI combination for treating advanced ccRCC.

Belzutifan cabozantinib combo shows durable anti-tumour effect at phase II for ccRCC

Dr Toni Choueiri - Dana-Farber Cancer Institute, Boston, USA

We’re very happy to present in the oral session the results of LITESPARK-003 which is a phase II study combining a TKI, cabozantinib, with a novel drug, novel mechanism of action, belzutifan, a HIF2 inhibitor. We had two cohorts, one is the untreated cohort, so no PD-1, just belzutifan cabozantinib, and then cohort 2 was the previously treated patients, up to two prior lines as long as one line is immunotherapy. We saw a response rate of 70% in cohort 1 and if you look at the favourable risk patients 79%. Toxicities were manageable, especially with dose interruptions and dose reductions. All patients, the 50 patients, experienced all tumour shrinkage. There was one patient who is PD because of a new lesion.

Now, in cohort 2 toxicity was not that different. We saw a response rate of 31% although the vast majority of patients, over 80%, had tumour shrinkage. The progression free survival was around 14 months, 13.8 in cohort 2, suggesting really an intriguing potential standard that could emerge of VEGF TKI plus HIF2 inhibition in patients previously treated.

Still, how we take the untreated patients, can we do it with PD-1, no PD-1 first line, remains to be seen. But it’s a proof of concept that combining a VEGF TKI in the situation cabozantinib with belzutifan is active and they could be combined.