NCT05636618

Targeted Alpha-Particle Therapy for Advanced Somatostatin Receptor Type 2 (SSTR2) Positive Neuroendocrine Tumors

A Phase I/IIa First-in-Human Study of [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 260 (estimated)
• Sponsor: Perspective Therapeutics · Industry
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

This study is Phase I/IIa First-in-Human Study of \[212Pb\]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors

Detailed description

This is a prospective, multi-center, open-label, radioactivity dose-finding/ dose expansion study of \[212Pb\]VMT-α-NET in up to 260 adult subjects with unresectable or metastatic SSTR2-expressing neuroendocrine tumors (NETs) who have not received prior peptide receptor radionuclide therapy (PRRT). Somatostatin Receptor type 2 (SSTR2) is highly expressed on various tumors including NETs and therefore is an attractive therapeutic target for NET treatment. Lead-212 (\[212Pb\]-) 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. \[212Pb\] VMT-a-NET is a targeted alpha therapy agent designed to enhance the precision and effectiveness of cancer treatment by delivering a highly potent form of radiation directly to cancer cells. This approach aims to maximize radiation delivery to tumors while minimizing exposure to healthy tissues. The study will be conducted in 2 parts: Part 1: Phase I Dose-Finding: Subjects will receive radioactive doses of \[212Pb\]VMT-α-NET up to a maximum dose of 222 MBq (6 mCi) for dose-limiting toxicity (DLT) observation, determining Optimal Biological Dose (OBD) and potential Recommended Phase 2 Dose (RP2D) for Part 2 (Dose Expansion). Dose changes or adjustments will be made by the safety monitoring committee (SMC) and Sponsor. The RP2D will be determined following a holistic analysis of observed DLTs, adverse events (AEs), estimated cumulative organ radiation exposure, and efficacy signals over the course of all treatment cycles for all dose cohorts. Part 2: Phase IIa Dose-Expansion: This part will enroll subjects who will receive RP2D identified in Part 1 for further assessment of safety and preliminary efficacy. Reno-protective amino acids will be co-administered prior to each \[212Pb\]VMT-α-NET dose in all subjects. Dose-finding will be based on an adaptive design until optimal biologic dose is identified or the pre-specified rules are met. A dosimetry sub-study using \[203Pb\]VMT-α-NET will be conducted. The subjects will undergo dosimetric evaluation prior to receiving the therapeutic agent.

Conditions

• Neuroendocrine Tumors Unresectable
• Neuroendocrine Tumor Metastatic
• Gastroenteropancreatic Neuroendocrine Tumor
• Bronchial Neuroendocrine Tumor
• Paraganglioma
• Pheochromocytoma

Interventions

Type	Name	Description
DRUG	[203Pb]VMT-α-NET	\[203Pb\]VMT-α-NET is administered by intravenous bolus injection for single-photon emission computed tomography imaging.
DRUG	[212Pb]VMT-α-NET	\[212Pb\]VMT-α-NET is administered by intravenous infusion for treatment of SSTR2 expressing neuroendocrine tumors.

Timeline

• Start date: 2023-09-27
• Primary completion: 2029-11-26
• Completion: 2029-12-26
• First posted: 2022-12-05
• Last updated: 2025-11-24

Locations

17 sites across 1 country: United States

Regulatory

• FDA-regulated drug study