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.
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
Active secondary malignancy
Prior systematic treatment with radioactive nuclides. Subjects who had localized treatment with radioactive nuclides or imaging using radioactive imaging agents may be enrolled
Pregnancy or breastfeeding a child
Any serious/active/uncontrolled infection requiring parenteral antibiotics within 2 weeks before the first administration of [212Pb]VMT01
Sequential
[203Pb]VMT01
Drug\[203Pb\]VMT01 is administered intravenous (IV) as an imaging agent for SPECT/CT
[212Pb]VMT01
DrugSubjects 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.
Nivolumab
DrugFor all combination-therapy cohorts, 480 mg nivolumab will be administered every 4 weeks as an IV infusion.
Number of subjects with dose-limiting toxicities (DLTs) after the first administration of [212Pb]VMT01 as a monotherapy or in combination with nivolumab.
DLTs describe side effects of a drug that are serious enough to prevent an increase in dose
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Percentage of subjects with complete responses (CRs) or partial responses (PRs) to at least 1 administration of \[212Pb\]VMT01 as a monotherapy or in combination with nivolumab
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) following administration of [212Pb]VMT01 as a monotherapy or in combination with nivolumab
Any untoward medical occurrence in a clinical investigational participant administered \[212Pb\]VMT01 as a monotherapy or in combination with nivolumab. Associated AE or SAE is assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Duration of response (DOR) following treatment with [212Pb]VMT01 as a monotherapy and in combination with nivolumab as assessed by RECIST v1.1 criteria
DOR is time interval between the onset of a treatment response and the subsequent progression of disease or death
Progression free survival (PFS) for subjects receiving at least one administration of [212Pb]VMT01 as a monotherapy and in combination with nivolumab, as assessed by RECIST v1.1 criteria
PFS a measure of how long a patient with a cancer lives without their cancer progressing or worsening.
Determination of pharmacokinetic properties (PK) of [212Pb]VMT01: Area under the concentration versus time curve
Blood radioactivity PK endpoint reported as Ci\*h/L
Determination of pharmacokinetic properties of [212Pb]VMT01]: Apparent terminal elimination half-life (T1/2)
Blood radioactivity PK endpoint (reported as time in minutes)
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