With new data out on Arcus Biosciences’ experimental HIF-2a inhibitor, one group of analysts figures the company could give Merck’s Welireg a run for its money in kidney cancer.
In the phase 1/1b ARC-20 study of Arcus’ candidate casdatifan in metastatic clear cell renal cell carcinoma (ccRCC), the biotech’s HIF-2a inhibitor achieved a general overall response rate (ORR) of 34%—with two responses pending confirmation—and a confirmed ORR of 25%.
The data come from a 100-mg daily-dose expansion cohort that enrolled ccRCC patients whose disease had progressed on at least two prior lines of therapy, including both an anti-PD-1 medicine and a tyrosine kinase inhibitor, Arcus said Thursday.
At the time of the study’s data cutoff point on Aug. 30, only 19% of patients had primary progressive disease, according to the biotech. Most patients instead experienced disease control with either a partial response or stable disease, Arcus said.
The median follow-up at that point in the study was 11 months. Median progression-free survival (PFS) had not been reached by the data cutoff, the company said.
In a note to clients Thursday, analysts at Evercore ISI shared optimism about Arcus’ data, noting that the biotech’s drug charted a “small, but meaningful, improvement in ORR” compared with a separate trial of Merck’s Welireg. While cross-trial comparisons carry inherent issues such as differences in trial populations and methodology, they're often used by analysts and others to weigh medicines against one another in the absence of head-to-head studies.
Welireg, which is also a hypoxia-inducible factor-2 alpha (HIF-2a) inhibitor, won its second FDA approval in relapsed or refractory renal cell carcinoma in December. The therapy was initially approved to treat the rare disease von Hippel-Lindau, which causes tumor growth in various organs, but most often in the kidneys.
In highlighting casdatifan’s potential versus Merck’s approved med, which achieved an ORR of 22.7% in the late-stage LITESPARK-005 study, the Evercore team noted that Arcus’ drug reached its ORR stats at both a later stage of disease and with a shorter follow-up.
The analysts also highlighted the “strong potential” of Arcus’ progressive disease data, which they called a “major driver of eventual PFS.”
With the data in hand, Arcus’ chief medical officer Dimitry Nuyten, M.D., Ph.D., said the company is now gearing up for a phase 3 trial for casdatifan plus Exelixis’ Cabometyx in the first half of 2025. The company also plans to expand its development program for the HIF-2a inhibitor into the first-line setting by wedding casdatifan with AstraZeneca’s experimental antibody volrustomig.
Under an existing collaboration pact, Gilead Sciences has the right to opt in to development and commercialization of casdatifan after Arcus’ delivery of a qualifying data package.
Given Thursday’s results, the Evercore team now expects Gilead is likely to join the fray either by the end of 2024 or the first quarter of 2025.
Up until now, Arcus’ partnership with Gilead has largely centered around TIGIT meds.
Gilead originally struck a far-reaching, 10-year deal with Arcus in 2020, paying $175 million upfront for rights to the PD-1 checkpoint inhibitor zimberelimab, plus options on the rest of Arcus’ pipeline. Gilead took up options on three Arcus programs the following year, handing the biotech another $725 million.
Back in January, Gilead and Arcus announced they were stopping a phase 3 lung cancer TIGIT trial. At the same time, Gilead revealed it would leave Arcus to run a late-stage study of the small-molecule CD73 inhibitor quemliclustat on its own.
Still, Gilead kept an interest in Arcus' work, with the Foster City, California-based pharma plugging a further $320 million into its biotech partner at the time. Arcus said early this year that it would use the cash, in part, to help fund its phase 3 trial of casdatifan in kidney cancer.