Arcus Biosciences (RCUS) Study Update summary

Study design and patient population

• ARC-20 is a Phase 1b/1 dose-escalation and expansion study of casdatifan (CAS), a HIF-2alpha inhibitor, in advanced or metastatic clear cell RCC, with dose escalation and expansion cohorts at 50 mg and 100 mg daily doses.

• The 100 mg daily dose (50 mg BID or QD) was selected for expansion; all patients had progressed on at least two prior therapies, including anti-PD-1 and VEGF TKI.

• 26–29% of patients had four or more prior lines of therapy; 52% had at least three.

• Baseline characteristics were similar to benchmark studies, with 61% of patients having an intermediate IMDC risk factor.

• Median follow-up at data cutoff was 11 months.

Efficacy results

• The 100 mg cohort showed an ORR of 34.4% (25% confirmed), disease control rate of 81.3%, and primary progression rate of 18.8–19%.

• The 50 mg cohort had an ORR of 25% (21.4% confirmed) and disease control rate of 85.7%.

• Median progression-free survival was not reached in either cohort at data cutoff; over 50% of patients remain progression-free.

• Most patients experienced tumor reduction, with deep and durable responses, including some lasting beyond one year.

• Efficacy compared favorably to belzutifan, despite a more heavily pretreated population and shorter follow-up.

Safety and tolerability

• CAS demonstrated a safety profile comparable to belzutifan, with similar rates of grade 3 or higher anemia (36–42%) and hypoxia (6–9%).

• No dose-limiting toxicities or grade 4 treatment-related adverse events were observed up to 150 mg; maximum tolerated dose not reached.

• Serious TEAEs occurred in 12–23% of patients, with very few leading to discontinuation.

• No treatment-related deaths or life-threatening TEAEs reported; no patients discontinued due to anemia.

• Safety profile supports further development and combination strategies.