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

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 intravenous therapy (e.g., chemotherapy or checkpoint inhibitors), or prior oral therapy (e.g.,proto-oncogene B-RAF or mitogen-activated extracellular signal-regulated kinase inhibitors) who demonstrate MC1R positivity during screening are eligible for enrollment, provided that they undergo a wash-out period of 21 days, or 7 days, respectively, prior to Cycle 1 Day 1 treatment with \[212Pb\]VMT01. * Presence of measurable disease by RECIST v1.1 assessed within 45 days prior to the first dose of \[212Pb\]VMT01 on Cycle 1 Day 1 * Ability to lie flat and still for up to two hours for imaging scans; moderate conscious sedation allowed if indicated * For females of reproductive potential: agree to use of highly effective contraception and refrain from donating eggs (ova, oocytes) for the purpose of reproduction starting from screening, during treatment with \[212Pb\]VMT01 and/or nivolumab, and for at …