Promising Phase 1 Data for Actinium-225 Presented at 2026 ASCO GU

At the 2026 ASCO Genitourinary Cancers Symposium, Fred Saad, MD, presented encouraging phase 1 data evaluating the actinium-225 compound in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC), highlighting both favorable tolerability and striking early efficacy signals.

Although the primary goal of the dose-escalation study was to determine the optimal dose, the results exceeded expectations. Investigators evaluated four weight-based dose levels—75, 100, 125, and 150 kilobecquerels per kilogram. Across all dose levels, no dose-limiting toxicities were observed, allowing escalation to the maximum planned dose. Only a few patients at the highest dose required dose reductions, and treatment discontinuations due to adverse events were rare.

The most common adverse event was xerostomia, affecting nearly 90% of patients; however, the vast majority of cases were grade 1 and reversible, with no grade 3 or 4 events reported. Other side effects, including fatigue and nausea, were generally low grade and manageable.

Efficacy findings were particularly notable given that participants were post–androgen receptor pathway inhibitor (ARPI) and post-taxane chemotherapy, placing them in the third-line setting or beyond. Across all dose levels, more than 60% of patients achieved a PSA decline of at least 50% (PSA50), with a substantial proportion reaching PSA90 responses. The 125 kilobecquerel/kg dose emerged as especially promising, producing PSA50 responses in 83% of patients and PSA90 responses in over 60%.

Responses were observed across standardized uptake value (SUV) levels, with the highest tertile (SUV >10) demonstrating a 93% PSA response rate. Complementary circulating tumor DNA (ctDNA) analyses reinforced these findings: at the 125 dose, 89% of patients experienced ctDNA reductions, and approximately 40% achieved complete clearance.

Based on these results, the 125 kilobecquerel/kg dose is being advanced into expansion cohorts, including chemotherapy-exposed patients, pre-chemotherapy patients post-ARPI, and a post-lutetium population—an area of significant unmet need. The data will inform the design of a forthcoming trial.