Targeted Alpha-Particle Therapy for Advanced Somatostatin Receptor Type 2 (SSTR2) Positive Tumors
Start Date
9/27/2023
Completion Date
12/26/2029
Summary
This study is Phase I/IIa First-in-Human Study of \[212Pb\]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive 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 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.
Eligibility Criteria
Age Range: 18 years to 90 years
Interventions
[203Pb]VMT-α-NET
[212Pb]VMT-α-NET
Conditions
Locations
Mayo Clinic
Jacksonville, Florida 32224
United States
Biogenix Molecular
Miami, Florida 33165
United States
Advent Health Radiation Oncology at Central Florida
Orlando, Florida 32804
United States
The University of Chicago
Chicago, Illinois 60637
United States
University of Iowa
Iowa City, Iowa 52242
United States
University of Kentucky
Lexington, Kentucky 40536
United States
Johns Hopkins
Baltimore, Maryland 21287
United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan 48201
United States
BAMF Health
Grand Rapids, Michigan 49503
United States
Michigan Health Professionals
Troy, Michigan 48098
United States
Mayo Clinic
Rochester, Minnesota 55905
United States
Washington University
St Louis, Missouri 63110
United States
Nebraska Cancer Specialists
Omaha, Nebraska 68130
United States
University of North Carolina
Chapel Hill, North Carolina 27599
United States
UH Cleveland Medical Center
Cleveland, Ohio 44106
United States
Ohio State University
Columbus, Ohio 43210
United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee 37232
United States
Virginia Cancer Specialists
Fairfax, Virginia 22031
United States
Fred Hutchinson Cancer Center
Seattle, Washington 98109
United States
Froedtert Medical College of Wisconsin
Milwaukee, Wisconsin 53226
United States