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

This is a prospective, multi-center, open-label, radioactivity dose-finding/ dose expansion study of \[212Pb\]VMT-α-NET in up to approximately 300 adult subjects with unresectable or metastatic SSTR2-expressing tumors who have not received prior peptide receptor radionuclide therapy (PRRT).

Somatostatin Receptor type 2 (SSTR2) is highly expressed on various tumors including Neuroendocrine tumors (NETs), meningioma and therefore is an attractive therapeutic target. 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 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 with gastroenteropancreatic NETS, bronchial NETS, pheochromocytoma or paragangliomas, and meningioma. Subjects 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.