Combined safety and efficacy results from three clinical studies evaluating alpha radiotherapy for advanced pancreatic cancer.

4215 Background: Pancreatic cancer (PDAC) remains associated with poor prognosis and limited treatment options, particularly in patients with advanced disease. Diffusing Alpha-Emitter Radiation Therapy (Alpha DaRT), a novel alpha-emitting radiation source, has shown initial clinical benefit in superficial epithelial solid tumors. The pooled studies presented here evaluated the safety and efficacy outcomes for endoscopic ultrasound (EUS)-guided alpha radiotherapy using Alpha DaRT in patients with PDAC. Methods: This analysis pooled data from three prospective clinical studies at 3 medical centers in Canada and Israel evaluating Alpha DaRT in patients with locally advanced or metastatic PDAC, regardless of previous lines of therapy. Primary outcome was safety, as assessed by CTCAE V5. Secondary outcomes were best overall response (BOR) of the primary tumor assessed per RECIST V1.1 and overall survival (OS), defined from Alpha DaRT treatment. Results: A total of 58 subjects (31 male, 27 female), median age 72 (range 41-91), were recruited between 2023 and 2025 across the three trials. Treatment-associated AEs of any grade occurred in 21 patients (36%). Grade ≥3 AEs occurred in 5 patients (9%) (biliary obstruction, abdominal pain, fever, liver enzyme imbalance and bacteremia). There were no treatment-related deaths and all grade ≥3 AEs resolved. Across all patients evaluable for response, the BOR showed a disease control rate of 87% and an objective response rate of 27%, with 3 complete and 9 partial responses. Median OS for the cohort was 7.9 months (95% CI: [6.1–11.6]): 10.4mo (95% CI: [7.3–13.4]) when given in 2nd line (N = 24) and 7.5 months (95% CI: [4.2–11.8]) when given in 3 rd line (N = 21). Conclusions: In this pooled analysis of three clinical studies, EUS-guided Alpha DaRT demonstrated a reassuring safety profile and promising early efficacy signals in patients with advanced PDAC. The observed survival outcomes and radiographic responses support further clinical investigation, which is underway. Clinical trial information: NCT04002479 ; NCT05781555 ; NCT05657743 .