LITESPARK-024 was a study that came out of Bill Kaelin’s lab at Dana-Farber Cancer Institute where they study, amongst other things, the impact of HIF-2 and HIF-2 blockade in both mouse models and other preclinical models. They were some of the first investigators to identify HIF-2 as a potential target, which led in part to the Nobel Prize in Medicine in 2019, and more importantly for our kidney cancer patients, the development of the first HIF-2α inhibitor belzutifan which is improving outcomes in kidney cancer, first as a single agent in patients who have failed multiple therapies but now, at this meeting, earlier in their disease, and now in combination with other drugs like VEGF and PD-1 now in the adjuvant setting. So we’re seeing two pivotal trials in those two settings with HIF-2 blockade.
This study came out of his lab where they actually associated CDK4/6 inhibition with a combination benefit in their mouse models, where if you combine CDK4/6 blockade with HIF-2 alpha blockade you could actually improve outcomes. Taking the drug they use, palbociclib, which is approved in breast cancer, and combining it with belzutifan.
We saw some interesting things. The study was designed as a part one, where we would dose-escalate the palbociclib, give full dose belzutifan, and see how patients did from a safety point of view, and we showed that you could give full doses of both drugs. Not that there wasn’t toxicity, because there certainly was, a lot of patients had grade 3 toxicity, but it was very manageable and no new toxicities were seen.
Importantly, at the highest dose level, we saw some interesting activity. Not from a response rate point of view, because the response rate was similar, just around 20%, to what you’d see with belzutifan alone, but the number of patients who had primary progression was much lower than you’d expect with belzutifan, disease control rate much higher, and progression-free survival much longer than you’d expect with single agent belzutifan. So while the sponsor of this study decided not to go forward with the randomised portion of this trial, the study suggests in my opinion that combination therapy that targets the tumour might have a future in kidney cancer. So much of what we’ve been doing now is targeting the microenvironment, but this is an approach which is dual-targeting the actual tumour cell. Maybe there are other approaches with other novel therapies that might offer hope in the future, and it’s a good direction, I think, for us to go in.
