A Phase I/IIa, First-In-Human, Multi-Center, Monotherapy and Combination-Therapy With Nivolumab, Dose-Finding and Dose-Expansion Study of [212Pb]VMT01 Melanocortin-1 Receptor-Targeted, Image-Guided Alpha-Particle Therapy in Subjects With Previously Treated Unresectable or Metastatic Melanoma
Perspective Therapeutics
Summary
In this first-in human, phase I/IIa study, the safety and efficacy of \[212Pb\]VMT01, an alpha-particle emitting therapeutic agent targeted to melanocortin sub-type 1 receptor (MC1R) is being evaluated as a monotherapy and in combination with nivolumab in subjects with unresectable and metastatic melanoma.
Description
This is a prospective, multi-center open-label dose-finding, dose-expansion study of \[212Pb\]VMT01 as a monotherapy or in combination with nivolumab in up to 300 subjects with histologically confirmed melanoma and a positive MC1R imaging scan with imaging agents \[203Pb\]VMT01 or \[68Ga\]VMT02. MC1R is a receptor that is expressed on the surface of melanoma cells and therefore is an attractive therapeutic target for melanoma treatment. Lead-212 (\[212Pb\]-) based peptide-radiopharmaceuticals are an emerging class of targeted alpha-particle cancer therapies that have potential to improve deli…
Eligibility
- Age range
- 18–90 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Ability to understand and willingness to provide informed consent, willingness to comply with all study procedures for the duration of the study * Aged ≥ 18 years * Diagnosed with unresectable Stage III or Stage IV metastatic or recurrent melanoma * Previously progressed (radiological progression) on at least one approved systemic therapy for advanced melanoma * Uptake of \[68Ga\]VMT02 or \[203Pb\]VMT01 by PET or SPECT imaging observed in at least one melanoma tumor site using quantitative imaging analysis compared to reference normal tissue * Subjects on prior intraveno…
Interventions
- Drug[203Pb]VMT01
\[203Pb\]VMT01 is administered intravenous (IV) as an imaging agent for SPECT/CT
- Drug[212Pb]VMT01
Subjects with positive uptake of \[203Pb\]VMT01 will receive a fixed dose of \[212Pb\]VMT01 administered IV every 8 weeks starting at Cycle 1 Day 1.
- DrugNivolumab
For all combination-therapy cohorts, 480 mg nivolumab will be administered every 4 weeks as an IV infusion.
Locations (13)
- University of California IrvineOrange, California
- Mayo ClinicJacksonville, Florida
- University of MiamiMiami, Florida
- Sarasota Memorial HospitalSarasota, Florida
- University of IowaIowa City, Iowa
- University of KentuckyLexington, Kentucky