Belzutifan Shows Continued Efficacy in Heavily Pretreated Advanced RCC

Eric Jonasch, MD, discusses the 3-year follow-up of the LITESPARK-001 trial of belzutifan in patients with clear cell renal cell carcinoma.

Eric Jonasch, MD, professor in the department of genitourinary medical oncology, division of cancer medicine at The University of Texas MD Anderson Cancer Center, discusses the 3-year follow-up of the LITESPARK-001 trial (NCT02974738) of belzutifan (Welireg) in patients with clear cell renal cell carcinoma (RCC).

The phase 1 trial found that the hypoxia-inducible factor 2α (HIF-2α) inhibitor belzutifan demonstrated efficacy and safety in a cohort of 55 patients with previously treated RCC. Updated data with more than 3 years of follow-up showed no new safety signals.

The objective response rate (ORR) was 25%, which was unchanged from previous analysis. Subset analyses showed an ORR of 31% in favorable-risk patients versus 24% in those with intermediate or poor risk.

Jonasch says investigators looked at response by prior therapy; those who had not received prior immunotherapy (IO) or VEGF–tyrosine kinase inhibitor (VEGF-TKI) had a better ORR of 38% versus only 21% for those who had received both of these classes of drugs. He says it was still notable for patients to respond despite receiving these prior therapies.

The median progression-free survival (PFS) was 14.5 months (95% CI, 7.3-22.1) with a PFS rate at 36 months of 34%. This shows belzutifan is active even in this heavily pretreated population, according to Jonasch. A phase 3 trial (NCT04195750) comparing belzutifan with everolimus (Afinitor) is currently ongoing for patients with advanced RCC.


0:08 | From an ORR perspective, we see that this has continued to hold up. The ORR in this follow-up of 41 months is 25%, as it was before, and there are some subset analyses that have been formed looking at whether or not this is different in favorable versus intermediate and poor risk. It doesn't look like there's a major difference; it's 31% in the [patients with] favorable risk, it’s 24% in the [patients with] intermediate/poor risk.

The other thing we looked at was needing 3 prior therapies received in this patient population, so heavily pretreated. Those who did not receive either prior IO or VEGF-TKI, the ORR was 38%. For those who had received prior IO and VEGF-TKI, the ORR was 21%. Again, small numbers in this but still very interesting to see that this is quite effective, regardless of what prior therapies people have received.

The median PFS was 14.5 months, so from a metastatic RCC perspective, we're seeing that even as a single agent in this heavily pretreated patient population, the data continue to hold up that this drug belzutifan is active in this patient population. There's a phase 3 randomized study against everolimus that has completed accrual and we're going to hopefully get a readout on that study in the next year or 2. I'm looking forward to seeing this being an approved agent in advanced RCC.