FDA Grants Fast Track Designation to VMT01 for Unresectable/Metastatic MC1R+ Melanoma

FDA

The FDA has granted fast track designation to the development of the targeted alpha-particle therapy (212Pb) VMT01 for the diagnosis and treatment of patients with unresectable or metastatic melanoma, as well as those who have demonstrated melanocortin 1 receptor (MC1R) expression, Perspective Therapeutics announced in a news release.¹

VMT01 is designed to target and deliver the alpha-emitting isotope 212Pb to tumor sites expressing MC1R, a protein that is often overexpressed in metastatic melanoma. This proprietary clinical-stage low molecular weight peptide can also be labeled with 203Pb to enable patient selection, diagnostic imaging, and dosimetry via SPECT imaging.²

VMT01 was previously evaluated in a completed pilot imaging study at the Mayo Clinic, in Rochester, Minnesota, and is currently being evaluated in a phase 1/2a study (NCT05655312).

“We are pleased with the FDA’s recognition of the need for additional treatment options for patients with metastatic melanoma,” Markus Puhlmann, MD, MBA, chief medical officer of Perspective Therapeutics, stated in a news release.¹ “We are dedicated to working closely with the agency to accelerate VMT01's clinical development. Having recently completed the observation period for dose-limiting toxicity in 7 patients enrolled in cohort 2 of our phase 1/2a study, we look forward to sharing safety observations with the Safety Monitoring Committee and in a scientific forum later this year. Additionally, pending institutional review board approval, we plan to open a VMT01/anti–PD-1 combination cohort.”

This first-in-human, multicenter, open-label, dose escalation and expansion study is investigating VMT01 for patients between 18 to 90 years of age with stage IV metastatic or stage III unresectable, MC1R-positive melanoma.^1-3 Patients are required to have progressed on at least 1 prior therapy, have uptake of [⁶⁸Ga]VMT02 or [²⁰³Pb]VMT01 by PET or SPECT imaging, show measurable disease per RECIST 1.1 criteria, and have an ECOG performance score of 0 or 1 at the time of screening.³

Exclusion criteria include active secondary malignancy, prior treatment with radioactive nuclides, active infection, or brain metastasis requiring acute therapy of any modality within 2 weeks of enrollment or clinical instability, including signs or symptoms of brain edema.

The dose-escalation phase of the study aims to determine the maximum tolerated dose or maximum feasible dose after a single administration of [²¹²Pb] VMT01. The dose expansion phase is designed to select the appropriate dose of [²¹²Pb] VMT01 for further clinical trials. Additionally, a dosimetry sub-study using the imaging surrogate [²⁰³Pb] VMT01 has been included to evaluate normal organ distribution, tumor uptake, estimate radiation dosimetry, and correlate these factors with observed toxicities and treatment efficacy.

In August 2023, Perspective Therapeutics announced that the first patient had been dosed in the study. Patient recruitment for the second dosing cohort was initiated in January 2024, following a unanimous recommendation from the study’s safety monitoring committee to move forward.²

References

1. Perspective Therapeutics granted fast track designation for VMT01 for the diagnosis and treatment of MC1R-positive melanoma. Perspective Therapeutics. News release. September 5, 2024. Accessed September 5, 2024. https://www.perspectivetherapeutics.com/newsroom/press-release?i=137680
2. Perspective commences recruitment for second dose escalation cohorts in clinical studies of two lead programs: [(212)Pb]VMT-α-NET and [(212)Pb]VMT01. Perspective Therapeutics. News release. January 17, 2024. Accessed September 5, 2024. https://www.perspectivetherapeutics.com/newsroom/press-release?i=130204
3. MC1R-targeted alpha-particle therapy trial in adults with advanced melanoma. ClinicalTrials.gov. Updated August 22, 2024. Accessed September 5, 2024. https://clinicaltrials.gov/study/NCT05655312