Casdatifan Exhibits 1+ Year Survival in Later-Line Kidney Cancer

Later-line treatment with the HIF-2α inhibitor casdatifan exhibited progression-free survival (PFS) exceeding 1 year among patients with metastatic clear cell renal cell carcinoma (ccRCC), according to findings from the phase 1/1b ARC-20 study.¹

After a median follow-up of 17.9 months among 31 patients treated with a 100 mg daily dose of casdatifan, the median PFS was 15.1 months (95% CI, 5.7-not evaluable [NE]), with respective 6- and 12-month rates of 68% (95% CI, 48%-81%) and 61% (95% CI, 42%-76%). In a pooled analysis of 121 patients, which included those treated with casdatifan at 50 mg twice daily, 50 mg daily, or 150 mg daily doses, the median PFS was 12.2 months (95% CI, 9.4-16.5) after a median follow-up of 20.8 months. The 6- and 12-month rates were 63% (95% CI, 54%-71%) and 51% (95% CI, 41%-60%), respectively.

Moreover, in the 100 mg and pooled analysis groups, the respective confirmed objective response rates (ORRs) were 45% (95% CI, 27%-64%) and 35% (95% CI, 26%-44%). All responses were partial responses (PRs) in the 100 mg, and all but 1 were PRs in the pooled analysis. The median time to response was 2.6 months vs 2.8 months, and the disease control rate (DCR) was 84% (95% CI, 66%-95%) vs 81% (95% CI, 73%-88%), in the 100 mg and pooled analysis arms, respectively.

“An analysis of data for casdatifan, a next-generation HIF-2α inhibitor, showed the majority of patients reached near-maximal serum erythropoietin [sEPO] reduction, and that deep and prolonged suppression was associated with better response and clinical benefit,” Toni K. Choueiri, MD, director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber, the Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School, and lead investigator of the ARC-20 trial, said in the news release.¹ “HIF-2α inhibition has emerged as a novel treatment that is changing the treatment paradigm for patients with ccRCC, and the results from ARC-20 are very encouraging.”

Patients in the phase 1/1b dose-escalation and expansion trial were assigned to 1 of 4 monotherapy cohorts, and they primarily experienced progression following at least 2 prior lines of therapy including an anti-PD-1 and VEGFR tyrosine kinase inhibitor (TKI). Those eligible for enrollment also had at least 1 measurable lesion per RECIST guidelines and an ECOG performance status score of 1 or lower.² Those excluded from trial enrollment included those with any use of live vaccines against infectious diseases within 4 weeks of study start, as well as those with a history of trauma or major surgery within 28 days prior to first study dose.

The primary end point of the study was dose-limiting toxicities and the incidence of adverse effects (AEs). Secondary end points included ORR, plasma concentration, area under the plasma concentration time curve, and maximum observed plasma concentration of casdatifan.

Findings revealed no unexpected signals and that casdatifan’s safety profile was generally manageable across all doses. Serious treatment-emergent AEs (TEAEs) occurred in 31% of the 100 mg group and 31% of the pooled analysis. The most common grade 3 or higher TEAEs in each of the respective groups included anemia (25% vs 41%) and hypoxia (9% vs 11%). A total of 9% vs 9% experienced TEAEs leading to discontinuation of study treatment, including 1 case (3%) of hypoxia in the 100 mg cohort and 3 cases (2%) of hypoxia in the pooled analysis.

The full data will be presented in a poster session at the 2026 American Society of Clinical Oncology Genitourinary Cancer (ASCO GU) Symposium.

References

1. Arcus presents new data for its HIF-2a inhibitor casdatifan, which showed progression-free survival beyond one year in late-line kidney cancer. News release. Arcus Biosciences. February 23, 2026. Accessed February 24, 2026. https://tinyurl.com/t89ncwvf
2. A phase 1 study of AB521 monotherapy and combination therapies in renal cell carcinoma and other solid tumors (ARC-20). ClinicalTrials.gov. Updated February 12, 2026. Accessed February 24, 2026. https://tinyurl.com/rjs2x5ke