Casdatifan Plus Cabozantinib Demonstrates Promising Efficacy in ARC-20 Study for Clear Cell Renal Cell Carcinoma

The ARC-20 study, a Phase 1/1b dose-escalation and expansion study, evaluated the efficacy and safety of casdatifan, a HIF-2a inhibitor, plus cabozantinib, a tyrosine kinase inhibitor, in patients with clear cell renal cell carcinoma (ccRCC) who had progressed on prior immunotherapy. Among the efficacy-evaluable population of 24 patients, 46% achieved a confirmed response per RECIST 1.1, with no primary progressive disease reported. The combination demonstrated a manageable safety profile, with no unexpected safety risks identified and minimal overlapping toxicity with each drug.

Key Takeaways:

• The combination of casdatifan and cabozantinib showed a confirmed overall response rate (ORR) of 46% in patients who reached a minimum of 12 weeks of follow-up in the ARC-20 study.
• The safety-evaluable population of 42 patients experienced an acceptable safety profile, with no meaningful overlapping toxicity between the two drugs.
• No unexpected safety risks were identified, and only two patients discontinued study treatment, with no casdatifan-related Grade 4 or 5 adverse events reported.
• The incidence of treatment-emergent adverse events (TEAEs) with casdatifan, particularly anemia and hypoxia, was similar to TEAEs observed with casdatifan monotherapy.
• The combination had a manageable safety profile, consistent with that of either agent alone, supporting their potential as a combination therapy.

Statistics:

• 46% of patients in the efficacy-evaluable population achieved a confirmed response per RECIST 1.1.
• The median follow-up was 5.3 months.
• 73% of patients had a confirmed partial response or a confirmed complete response or stable disease.
• 42% of patients experienced partial response, with one patient having primary progressive disease.
• 50% of patients achieved stable disease.
• 24% of patients experienced treatment-related Grade 3 adverse events, with anemia reported in 10% of patients.
• 5% of patients experienced hypoxia related to casdatifan.
• 2% of patients discontinued treatment due to adverse events.

Sources:

• Arcus Biosciences news release, "Arcus Presents Initial Clinical Data for Casdatifan in Combination with Cabozantinib in Immunotherapy-Experienced Patients with Clear Cell Renal Cell Carcinoma at the 2025 ASCO Annual Meeting", June 1, 2025.
• Abstract presentation by Dr. Toni K. Choueiri at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
• Arcus Biosciences website: www.arcusbio.com.