FDA Grants Fast Track Designation to PSV359 for Advanced FAP-Positive Solitary Fibrous Tumors

The FDA has granted fast track designation to [²¹²Pb]PSV359 for the treatment of adult patients with locally advanced unresectable or metastatic FAP-positive solitary fibrous tumors.¹

Preclinical studies have shown FAP-targeted tracer uptake in solitary fibrous tumor models. In previously reported findings for first-in-human SPECT/CT imaging, ²⁰³Pb–labeled PSV359 demonstrated tumor uptake, prolonged tumor retention, rapid clearance through the kidneys, and low accumulation in normal organs in 3 patients with FAP-expressing cancers.²

PSV359 delivering ²¹²Pb is being investigated in an ongoing phase 1/2a study (NCT06710756) in patients with advanced FAP-positive solid tumors.^1,3 At the 2026 ASCO Annual Meeting, findings reported from the study showed no dose-limiting toxicities and only grade 1 or 2 treatment-emergent adverse effects (AEs) as of the December 24, 2025, data cutoff.⁴ According to an August 2026 update, 17 patients had received PSV359 across 3 dose cohorts as of July 31, 2026.⁵ Cohort 3 opened and closed during the second quarter of 2026, and the next clinical update is planned for 2027.

“FAP-α is a particularly compelling target because of its broad expression across solid tumors and within the tumor microenvironment, creating the potential for PSV359 to address a substantial patient population across multiple cancer types,” Markus Puhlmann, MD, MBA, chief medical officer of Perspective Therapeutics, stated in a news release.¹ “There are currently no approved therapies specifically targeting FAP-α, despite its association with aggressive cancers and tumor environments that can limit drug penetration and suppress immune activity. Imaging FAP-α expression before treatment allows us to pair patient selection with targeted alpha radiopharmaceutical therapy and pursue that broad opportunity with precision.”

What is the mechanism of action of PSV359?

PSV359 incorporates a peptide designed to bind FAP-α and a proprietary chelator that binds lead isotopes. The platform pairs lead-203 for single-photon emission computed tomography (SPECT) imaging with lead-212 for alpha-particle therapy. This approach allows investigators to visualize the target using an imaging agent and subsequently deliver therapeutic radiation using the corresponding treatment agent.

How is the ongoing phase 1/2a trial designed?

The ongoing phase 1/2 trial is evaluating PSV359 in patients at least 18 years of age with FAP-positive locally advanced or metastatic solid tumors.³ To be considered FAP-positive, patients must have a positive ²⁰³PbPSV359 SPECT/CT scan, showing uptake on at least 1 lesion. Other key enrollment criteria comprise satisfactory organ function, an ECOG performance status of 0 or 1, and a life expectancy of at least 3 months.

Patients with known brain metastases, active or uncontrolled infections requiring antifungals or antibiotics, or a diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to enrollment are being excluded.

The prospective, multicenter, open-label study consists of dose-escalation and dose-expansion portions and has an estimated enrollment of 112 patients. Four dose-level cohorts are planned during escalation, with patients assigned sequentially. This portion is designed to identify the maximum tolerated radioactivity dose and a potential recommended phase 2 dose. Expansion cohorts will evaluate doses selected for further clinical development.

Primary outcomes include the safety and tolerability of both the imaging and therapeutic agents, measured through the incidence and severity of treatment-related AEs, and determination of the recommended phase 2 dose.

Secondary outcomes include duration of response and progression-free survival assessed using RECIST 1.1 criteria, pharmacokinetics, and biodistribution.

“Fast track designation for FAP-positive solitary fibrous tumors is an important step in advancing the broader PSV359 program and our strategy of engineering targeted radiopharmaceutical therapy based on the alpha-generating isotope ²¹²Pb to optimize the therapeutic window in oncology,” Thijs Spoor, chief executive officer of Perspective Therapeutics, added in a news release.¹ “We look forward to working with the FDA and the medical community to define an efficient development path for PSV359 in this rare and serious disease.”

References

1. Perspective Therapeutics granted fast track designation for [212Pb]PSV359 for the treatment of adult patients with locally advanced unresectable and/or metastatic FAP-positive solitary fibrous tumors. News release. Perspective Therapeutics. October 8, 2026. Accessed October 9, 2026. https://perspectivetherapeutics.com/pr/perspective-therapeutics-granted-fast-track-designation-for-212pbpsv359-for-the-treatment-of-adult-patients-with-locally-advanced-unresectable-andor-metastatic-fappositive-solitary-fibrous-tumors
2. Perspective Therapeutics presents updates at the 37th Annual Congress of the European Association of Nuclear Medicine. News release. Perspective Therapeutics. October 23, 2024. Accessed October 9, 2026. https://perspectivetherapeutics.com/pr/perspective-therapeutics-presents-updates-at-the-37th-annual-congress-of-the-european-association-of-nuclear-medicine
3. Lead-212 PSV359 therapy for patients with solid tumors. ClinicalTrials.gov. Updated October 7, 2026. Accessed October 9, 2026. https://clinicaltrials.gov/study/NCT06710756
4. Perspective Therapeutics to present data from all clinical programs at the 2026 ASCO Annual Meeting, including findings from [212Pb]VMT01 in melanoma. News release. Perspective Therapeutics. May 21, 2026. Accessed October 9, 2026. https://perspectivetherapeutics.com/pr/perspective-therapeutics-to-present-data-from-all-clinical-programs-at-the-2026-asco-annual-meeting-including-findings-from-212pbvmt01-in-melanoma
5. Perspective Therapeutics provides recent business highlights and reports 2Q 2026 results. News release. Perspective Therapeutics. August 10, 2026. Accessed October 9, 2026. https://perspectivetherapeutics.com/pr/perspective-therapeutics-provides-recent-business-highlights-and-reports-2q-2026-results