MC1R-targeted Alpha-particle Monotherapy and Combination Therapy Trial With Nivolumab in Adults With Advanced Melanoma

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 delivery of a highly effective form of radiation. This study will be conducted in 3 parts: Part 1: Monotherapy Dose-Finding Part 2: Combination-Therapy Dose-Finding Part 3: Dose Expansion Enrolled subjects in Monotherapy may receive up to 3 doses of \[212Pb\]VMT01 approximately 8 weeks apart and subjects in combination therapy may receive up to 3 doses of \[212Pb\]VMT01 along with nivolumab. Nivolumab will be administered every 4 weeks for up to 24 months. A Dosimetry sub-set utilizing an imaging surrogate, \[203Pb\]VMT01, has been incorporated into the study in order to assess organ biodistribution and tumor uptake of the investigational products. This study will also estimate radiation dosimetry and correlate uptake of the investigation products with observed toxicities and efficacy.