Casdatifan Holds Patients Past a Year, and Arcus Now Has the Biomarker to Explain Why
Patients with metastatic clear cell renal cell carcinoma who had already progressed through multiple standard regimens went a median of 12.2 months without further progression on casdatifan, the investigational HIF-2α inhibitor from Arcus Biosciences (NYSE: RCUS). In the 100mg once-daily tablet cohort, the dose carried into Phase 3, a later data cut put median progression-free survival at 15.1 months. More than half those patients had received at least three prior lines of therapy.
Research published in Nature on July 1 goes further than the response numbers. It ties them to a measurable signal in the blood.
A biomarker, not just a response rate
Casdatifan suppressed serum erythropoietin deeply and durably across four monotherapy cohorts of the ARC-20 platform study, and the depth of that suppression tracked with higher response rates and longer progression-free survival. Tumors with high HIF-2α pathway activity at baseline also fared better on treatment.
That matters more than another efficacy line. A marker that moves early and predicts outcome gives a developer something to select patients on and something to dose against.
The clinical numbers came from a heavily pretreated group. Across 121 patients, 55% had received at least three prior lines of therapy and 29% had received at least four. Confirmed objective response rate was 31% and median progression-free survival was 12.2 months. In the 100mg once-daily tablet cohort, response rate was 35% and 60% of patients remained progression-free at 12 months.
Toni Choueiri of Dana-Farber, the study’s lead investigator, noted that patients achieved median progression-free survival beyond a year “despite half of patients having progressed on three or more prior treatments with other standard therapies.”
Building combinations before the pivotal readout
Three weeks later, Arcus added two cohorts to the same platform study. One pairs casdatifan with ivonescimab, the PD-1/VEGF bispecific from Summit Therapeutics (Nasdaq: SMMT), with initial data expected by mid-2027. The other, a clinical supply agreement with AVEO Oncology, randomizes casdatifan plus tivozanib against tivozanib alone in patients who already progressed on a HIF-2α inhibitor. Arcus expects enrollment to begin in the fourth quarter.
Neither deal carries licensing economics. Each partner supplies its molecule and keeps its rights, and Arcus runs the trial. The company says it expects to complete enrollment in PEAK-1, the Phase 3 testing casdatifan plus cabozantinib against cabozantinib in immunotherapy-experienced patients, and to start a first-line Phase 3 by year end.
What comes next
The Nature work comes from single-arm monotherapy cohorts, which is why the biomarker finding carries the weight it does. Linking EPO suppression to response and progression-free survival gives Arcus something to select and dose against heading into randomized studies. Richard Markus, chief medical officer at Arcus, called the research evidence that casdatifan is best-in-class. PEAK-1 is the study that puts a comparator behind that.
Arcus is assembling the combination footprint in parallel rather than waiting. First-line, second-line, and post-HIF-2α cohorts are all running or planned inside one platform study. Management will discuss second-quarter results and pipeline updates on an August 5 conference call. The kidney cancer data arrives through 2027.
