Phase 1b ARC-20 Trial Results for mCCRCC
Arcus presented updated results from the Phase I/Ib ARC-20 clinical trial of casdatifan in patients with metastatic ccRCC, most of whom progressed after two or more prior rounds of therapy, at the 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium
The data showed even greater differentation from Merck & Co.’s first-in-class HIF-2a inhibitor Welireg (belzutifan) than the company reported in an earlier update in October. median of 15 months of follow up. With median follow up of 12 months in the 50mg once daily group and five months in the 100mg once daily group, PFS has not yet been reached. The confirmed overall response rate (ORR) to date is 25% for 50mg twice daily, 32% for 50mg once daily and 33% for 100mg once daily. Median time to response was 2.8 months, 4.1 months and 1.6 months, respectively. The disease control rate (DCR) was 81% for 50mg twice daily, 86% for 50mg once daily and 85% for 100mg once daily. In terms of safety, rates of serious treatment-emergent adverse events (TEAEs) related to casdatifan were 3% for 50mg twice daily, 10% for 50mg once daily and 7% for 100mg once daily. Grade 3 or higher TEAEs related to casdatifan, which also have been associated with Welireg, were anemia – 42% for 50mg twice daily, 32% for 50mg once daily and 17% for 100mg once daily – and hypoxia at rates of 9%, 7% and 10%, respectively.
ARC-20 Data Support Phase III Plans; The ARC-20 study data presented at ASCO GU included results for casdatifan dosed at 50mg twice daily, 50mg once daily and 100mg once daily. The latter dose was selected for the planned Phase III PEAK-1 pivotal study testing the drug in combination with Exelixis’s tyrosine kinase inhibitor (TKI) Cabometyx (cabozantinib) versus cabozantinib monotherapy in first- or second-line treatment of metastatic ccRCC patients who previously were treated with an anti-PD-1 therapy. The primary endpoint will be progression-free survival (PFS) with overall survival as a key secondary endpoint. Arcus plans to initiate PEAK-1 in the second quarter of 2025, while in mid-2025 it will present initial safety and efficacy data from the Phase I/Ib ARC-20 cohort testing casdatifan in combination with cabozantinib, giving some insight into what data from the Phase III trial may look like.
Arcus also plans to share data from multiple ARC-20 cohorts in the fall of 2025 and share initial data from the Phase I/Ib trial in 2026 from newly initiated cohorts, including casdatifan monotherapy in favorable risk first-line ccRCC, casdatifan combined with Arcus/Gilead’s PD-1 inhibitor zimberelimab in first-line ccRCC and casdatifan monotherapy in immuno-oncology (IO) drug-experienced/TKI-naïve ccRCC. In addition, Arcus expects its clinical trial collaborator AstraZeneca to begin a Phase Ib trial in 2025 testing casdatifan in combination with the big pharma’s anti-PD-1/CTLA-4 bispecific antibody volrustomig in IO-naïve ccRCC patients.
Arcus’s clinical trial expansion plans are informed by the ARC-20 trial results to date, which in the recent update showed 9.7 months of PFS for patients treated with 50mg twice daily with a median of 15 months of follow up. With median follow up of 12 months in the 50mg once daily group and five months in the 100mg once daily group, PFS has not yet been reached. The confirmed overall response rate (ORR) to date is 25% for 50mg twice daily, 32% for 50mg once daily and 33% for 100mg once daily. Median time to response was 2.8 months, 4.1 months and 1.6 months, respectively. The disease control rate (DCR) was 81% for 50mg twice daily, 86% for 50mg once daily and 85% for 100mg once daily.
In terms of safety, rates of serious treatment-emergent adverse events (TEAEs) related to casdatifan were 3% for 50mg twice daily, 10% for 50mg once daily and 7% for 100mg once daily. Grade 3 or higher TEAEs related to casdatifan, which also have been associated with Welireg, were anemia – 42% for 50mg twice daily, 32% for 50mg once daily and 17% for 100mg once daily – and hypoxia at rates of 9%, 7% and 10%, respectively.
By comparison, Arcus noted that in the Phase III LITESPARK-005 trial of Welireg, the confirmed ORR rate was 22% with a DCR of 61% and median PFS of 5.6 months. Rates of grade 3 and higher anemia and hypoxia were 33% and 11%, respectively.
“Initial looks at this data seem very strong, and increasingly differentiated versus Merck,” Evercore ISI analyst Umer Raffat said in a 17 February note.
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