Optimal Casdatifan Dose for Heavily Pretreated Patients With HIF2α-Inhibitor–Naive Clear Cell Renal Cell Carcinoma
According to results from the phase 1 ARC-20 trial, 100 mg of casdatifan, a HIF-2α inhibitor, is preferable to 50 mg among heavily pre-treated patients with clear cell renal cell carcinoma (ccRCC).
These results were presented by Toni Choueiri, MD, Dana-Farber Cancer Institute, Boston Massachusetts, at the 2025 ASCO Genitourinary Cancers Symposium in San Francisco, California.
In this open-label study, researchers enrolled 60 HIF2α-inhibitor–naive patients previously treated with anti–PD-L1 and VEGFR tyrosine kinase inhibitor (TKI) therapies to receive 50 mg of casdatifan either once (dose escalation n = 1; dose expansion n = 31) or twice daily (dose escalation n = 3; dose expansion n = 50). Patients were identified as either IMDC favorable (n = 15) or IMDC intermediate/poor/unknown (n = 45). Primary end points included objective response rate (ORR), disease control rate, and safety.
At analysis, confirmed ORR was 21% in the 50 mg arm and 25% in the 100 mg arm. The disease control rate was 86% and 81%, respectively. The confirmed ORR was 33% for IDMC favorable patients and 20% for IMDC intermediate/poor/unknown patients. The disease control rate was 93% and 80%, respectively. Grade ≥3 treatment-related adverse events were observed in 42% of patients in the 50 mg arm and 36% of patients in the 100 mg arm. Grade 3 anemia was observed in 36% of patients regardless of dose. Grade 3 hypoxia was observed in 9% of patients in the 50 mg arm and 6% of patients in the 100 mg arm. No grade ≥4 treatment-emergent adverse events were reported.
“In heavily pretreated [patients] with ccRCC, [casdatifan] monotherapy was well tolerated with promising early clinical activity across IMDC risk groups,” concluded Dr Choueiri et al. “[Casdatifan] 100 mg QD will be combined with VEGFR-TKI (cabozantinib) in the phase 3 PEAK-1 trial and immunotherapy (volrustomig) in a separate upcoming first-line trial.”
Source:
Choueiri T, Lee JL, Merchan J, et al. Casdatifan (Cas) monotherapy in patients (pts) with previously treated clear cell renal cell carcinoma (ccRCC): Safety, efficacy and subgroup analysis across multiple doses from ARC-20, a phase 1 open-label study. Presented at the 2025 ASCO Genitourinary Cancers Symposium. San Francisco, California. February 13-15, 2025. Abstract 441
