A phase I/IIa, image-guided, alpha-particle therapy study of [ ²⁰³ Pb]Pb-PSV359 and [ ²¹² Pb]Pb-PSV359 in patients with solid tumors that are known to be fibroblast activation protein (FAP)–positive.

Abstract

e15146 Background: PSV359 is a novel theranostic radiopharmaceutical targeting fibroblast activation protein alpha (FAP-α), which is overexpressed in multiple solid tumors. PSV359 is designed for the delivery of targeted alpha-particle therapy, utilizing 203 Pb for SPECT imaging and ²¹²Pb for targeted radiotherapy. Here, we present preliminary data on the treatment of adult patients diagnosed with solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists. Methods: This is an ongoing phase I/IIa, first-in-human, prospective, multicenter, open-label, dose-escalation and dose-expansion trial. The objectives are to investigate the safety, dosimetry, pharmacokinetics, and efficacy of [²¹²Pb]Pb-PSV359. The trial follows a modified Toxicity Probability Interval-2 study design. The phase I portion includes escalating dose cohorts starting at 2.5 mCi (92.5 MBq) [²¹²Pb]Pb-PSV359 and increasing sequentially to determine the recommended phase II dose. Each dose level is given in up to 4 cycles, 8 weeks apart, by intravenous infusion. Safety is evaluated for any DLTs during cycle 1 according to the Common Terminology Criteria for Adverse Events, v5.0, and efficacy by RECIST v1.1 criteria by the investigator. Results: As of 24 December 2025, 6 participants (50% male; median age: 68.5 years [range: 62-74]) with locally advanced or metastatic solid tumors (kidney [n = 3], pancreatic ductal adenocarcinoma [n = 1], ovarian [n = 1], esophageal [n = 1]) were enrolled. All patients had at least 2 prior lines of systemic therapy. No DLTs were reported, no dose reductions were required, and TEAEs were all grade 1 and 2 (40% each). Patient enrollment is ongoing, and updated results may be presented at the meeting. One participant withdrew before receiving therapy due to disease progression. The remaining participants received at least 1 dose of either 2.5 or 5 mCi [²¹²Pb]Pb-PSV359. Two participants reported SD as best response, and one was not evaluable for response due to pending scans. Conclusions: The dose levels of 2.5 and 5 mCi [²¹²Pb]Pb-PSV359 were found to be safe without DLTs. Dose-escalation is ongoing. Clinical trial information: NCT06710756 .