Perspective Therapeutics is set to escalate the dosage of [212Pb]VMT-α-NET in its ongoing Phase 1/2a clinical trial after promising initial results presented at the 2024 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium. The study focuses on patients with unresectable or metastatic somatostatin receptor type 2 (SSTR2)-positive neuroendocrine tumors (NETs) who have not previously undergone radiopharmaceutical therapy (RPT).
The Phase 1/2a trial is designed as a multi-center, open-label, dose-escalation and dose-expansion study. Initial data, with a cutoff date of October 31, 2024, revealed that eight out of nine patients completed all four planned treatment doses.
Safety and Efficacy Observations
The trial has demonstrated a favorable safety profile for [212Pb]VMT-α-NET. No dose-limiting toxicities (DLTs) were observed at the tested doses of 2.5 and 5.0 mCi. Furthermore, there were no grade 4 or 5 treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs). Two grade 3 adverse events, one case of diarrhea and one of syncope, were reported. Hematologic adverse events, such as decreased lymphocyte count and anemia, were all grades 1 and 2, with no treatment discontinuations due to adverse events.
In terms of efficacy, eight of nine patients achieved durable disease control. Six patients experienced a measurable reduction in tumor volume, with one patient exhibiting a confirmed response according to RECIST v1.1 criteria. Notably, the anti-tumor activity appeared more pronounced in patients with lower body weight.
Dose Escalation Strategy
Based on these findings, the Safety Monitoring Committee (SMC) has recommended proceeding with dose escalation to Cohort 3 and expanding the number of patients dosed at 5 mCi. Perspective Therapeutics plans to consult with the FDA before opening Cohort 3, aligning with prior agreements.
Richard L. Wahl, MD, Professor of Radiology at Washington University School of Medicine, noted the well-tolerated safety and appreciable activity of [212Pb]VMT-α-NET, supporting the continuation of dose escalation.
About VMT-α-NET
VMT-α-NET is a targeted alpha-particle therapy (TAT) radiopharmaceutical in clinical development for SSTR2-expressing neuroendocrine tumors (NETs). It utilizes Perspective's proprietary lead-specific chelator (PSC) to bind 203Pb for SPECT imaging and 212Pb for alpha particle therapy. The FDA has granted Fast Track Designation to this program based on preclinical data for SSTR2-positive NETs, irrespective of prior treatment response.
Neuroendocrine Tumor Landscape
Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms arising from neuroendocrine cells. They can occur in various locations throughout the body, with the gastrointestinal tract and lungs being the most common sites. NETs are relatively rare, with an estimated incidence of over 12,000 new cases per year in the United States. However, due to their often indolent nature, the prevalence is much higher, with over 170,000 individuals living with NETs in the U.S.
