Lead-212 PSV359 Therapy for Patients With Solid Tumors

Phase 1

Recruiting

• Conditions: Pancreatic Ductal Adenocarcinoma; Gastric Cancer; Esophageal Cancer; Colorectal Cancer; Head and Neck Cancer; Ovarian Cancer
• Interventions: Drug: [203Pb]Pb-PSV359; Drug: [212Pb]Pb-PSV359

• Registration Number: NCT06710756
• Lead Sponsor: Perspective Therapeutics

Brief Summary

Phase I/IIa clinical study evaluating the safety and efficacy of peptide-based theranostic (therapeutic and diagnostic) radiopharmaceuticals, i.e. \[203Pb\]Pb-PSV359 and \[212Pb\]Pb-PSV359 targeting Fibroblast Activation Protein in subjects with solid tumors.

Detailed Description

This is a prospective, multi-center open label dose finding, dose expansion study of \[212Pb\]Pb-PSV359 in subjects with a positive Fibroblast Activation Protein (FAP) imaging scan with imaging agent.

FAP is specifically expressed on the surface of cancer-associated fibroblasts in some tumor tissues and therefore is an attractive target in the diagnosis and treatment of various cancers. Lead-212 (\[212Pb\]Pb-) based peptide-radiopharmaceuticals are an emerging class of targeted alpha-particle cancer therapies that have potential to improve delivery of a highly effective form of radiation.

This study will be conducted in 2 parts:

Part 1: Dose-escalation: \[212Pb\]Pb-PSV359 is administered in escalating doses to determine the Maximum Tolerated radioactivity (MTD) Dose and potential recommended Phase 2 dose (RP2D).

Part 2: Dose-expansion: This part will enroll subjects in expansion cohorts based on the identified MTD and RP2D for the selection of \[212Pb\]Pb-PSV359 doses for further clinical development.

A Dosimetry sub-study utilizing an imaging surrogate, \[203Pb\]Pb-PSV359, has been incorporated into the study in order to assess organ biodistribution and tumor uptake of the investigational products. This sub study will also estimate radiation dosimetry and correlate uptake of the investigation products with observed toxicities and efficacy.

Study Timeline

• Study First Submitted: 2024-11-25
• Study First Submitted QC: 2024-11-26
• Study First Posted: 2024-11-29
• Study Start: 2025-04-28
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-23
• Primary Completion: 2028-01-31
• Study Completion: 2032-05-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

• Aged ≥ 18 years
• Satisfactory organ function as determined by laboratory testing
• Eastern Cooperative Oncology Group performance (ECOG) status of 0 to 1
• Life expectancy > 3 months
• Progressive disease despite standard therapy or for whom no standard therapy exists
• Positive [203Pb]Pb-PSV359 SPECT/CT scan showing uptake of [203Pb]Pb-PSV359 in at least 1 known lesion on the 1-hour SPECT/ CT scan
• Histological, pathological, and/or cytological confirmation of solid tumor malignancy that is locally advanced or metastatic

Exclusion Criteria

• Known hypersensitivity to the active agent or any of the excipients
• Active secondary malignancy
• Pregnancy or breastfeeding a child
• Known brain metastases
• Known active or uncontrolled infections requiring ongoing antifungals or antibiotics in the 3 days prior to enrollment
• Known medical condition which would make this protocol unreasonably hazardous for the patient
• Existence of any medical or social issues likely to interfere with study conductor that may cause increased risk to the subject or to others, e.g., lack of ability to follow radiation safety precautions
• Medical history of a condition resulting in a severe allergic reaction such as anaphylaxis or angioedema to known components of the investigational product or excipients
• Major surgery within 21 days prior to the administration of [212Pb]Pb-PSV359; the subject must be sufficiently recovered and stable before treatment administration
• Diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to enrollment into the study
• Current abuse of alcohol or illicit drugs
• Treatment with any live/attenuated vaccine in the 7 days prior to enrollment
• Previous treatment with any systemic anticancer therapy within 4 weeks prior to treatment on study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation	[203Pb]Pb-PSV359	* Enrolled subjects are administered \[203Pb\]Pb-PSV359 (7mCi) for imaging FAP-expressing cancers. * Enrolled subjects are administered \[212Pb\]Pb-PSV359 (starting at 2.5 mCi upto 10 mCi) for treatment of FAP-expressing cancers and for determining Recommended Phase 2 Dose (RP2D)
Dose Escalation	[212Pb]Pb-PSV359	* Enrolled subjects are administered \[203Pb\]Pb-PSV359 (7mCi) for imaging FAP-expressing cancers. * Enrolled subjects are administered \[212Pb\]Pb-PSV359 (starting at 2.5 mCi upto 10 mCi) for treatment of FAP-expressing cancers and for determining Recommended Phase 2 Dose (RP2D)
Dose Expansion	[203Pb]Pb-PSV359	* Enrolled subjects are administered \[203Pb\]Pb-PSV359 (7mCi) for imaging FAP-expressing cancers. * Enrolled subjects are administered \[212Pb\]Pb-PSV359 (RP2D determined previously) for treatment of FAP-expressing cancers
Dose Expansion	[212Pb]Pb-PSV359	* Enrolled subjects are administered \[203Pb\]Pb-PSV359 (7mCi) for imaging FAP-expressing cancers. * Enrolled subjects are administered \[212Pb\]Pb-PSV359 (RP2D determined previously) for treatment of FAP-expressing cancers

Primary Outcome Measures

Name	Time	Method
Determination of safety and tolerability of [203Pb]Pb-PSV359	Up to 3 years	Incidence and severity of treatment-related adverse events following a single administration of \[203Pb\]Pb-PSV359 is determined
Determination of safety and tolerability of [212Pb]Pb-PSV359	Up to 3 years	Incidence and severity of treatment-related adverse events following a single and each repeated administration of \[212Pb\]Pb-PSV359 is determined
Determination of an antitumor efficacy of [212Pb]Pb-PSV359	Up to 3 years	The objective response rate (proportion of subjects with complete response or partial response) in dose expansion cohort for subjects receiving at least 1 administration of \[212Pb\]Pb-PSV359 is determined

Secondary Outcome Measures

Name	Time	Method
Determination of pharmacokinetic properties of [203Pb]Pb-PSV359 and [212Pb]Pb-PSV359	Up to 3 years	Blood radioactivity pharmacokinetic parameter such as the time (Tmax) to reach the maximum concentration (Cmax) is determined
Estimation of biodistribution of 203Pb PSV 359 using SPECT/CT scans	Up to 3 years	Activity in tumor(s) and organs as percentage of injected dose is assessed
Determination of duration of response following treatment with [212Pb]Pb-PSV359	Up to 3 years	Median duration of response for subjects receiving at least 1 administration of \[212Pb\]Pb-PSV359 is assessed by RECIST V1.1 criteria
Determination of progression free survival following treatment with [212Pb]Pb-PSV359	Up to 3 years	Progression free survival for subjects receiving at least 1 administration of \[212Pb\]Pb-PSV359 is assessed by RECIST V1.1 criteria

Trial Locations

Locations (1)

Nebraska Cancer Specialists; 🇺🇸 Omaha, Nebraska, United States