Overview

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 in patients with unresectable and metastatic melanoma.

Eligibility

Inclusion Criteria:

• Ability to understand and willingness to provide informed consent, willingness to comply with all study procedures for the duration of the study
• Male or female, aged ≥ 18 years
• Diagnosed with Stage IV metastatic melanoma, or unresectable Stage III
• Previously progressed (clinical or radiological progression) on at least one prior therapy for metastatic 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., BRAF or MEK inhibitors) who demonstrate MC1R positivity during screening are eligible for enrollment, provided that they undergo a wash-out period of 21 days, or 14 days, respectively, prior to Day 1 treatment with [212Pb]VMT01.
• Presence of measurable disease by RECIST v1.1 criteria assessed within 30 days prior to the start of 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: use of highly effective contraception for at least one month prior to screening, and agreement to use such a method during study participation and for an additional four weeks after the last administration of an investigational product
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional four weeks after the last administration of an investigational product
• ECOG performance score of < 2 at Screening
• Life expectancy of at least 3 months
• Evidence of sufficient organ function as determined by all of the following:

        Oxygen saturation > 90% on room air eGFR > 50 mL/min/1.73m2 by CKD-EPI equation Complete
        blood count with differential, within 7 calendar days prior to therapy and off Growth
        Factors White blood cells (WBC) > 2500/mm3 Hemoglobin (Hgb) > 9.0 g/dL Platelets >
        60,000/mm3 Absolute Neutrophil Count (ANC) > 1,250/mm3
        The comprehensive metabolic panel, within seven calendar days prior to Day 1, demonstrating
        values within the site's upper limit of normal (ULN), with the following exceptions:
        Alanine aminotransferase (ALT) < 3x ULN Aspartate aminotransferase (AST) < 3x ULN Alkaline
        phosphatase (ALP) < 2.5x ULN
        Exclusion Criteria:
          -  Active secondary malignancy
          -  Prior treatment (for any reason) with radioactive nuclides; however, imaging tracers
             are acceptable
          -  Pregnancy or breastfeeding a child
          -  Active infection
          -  Brain metastasis requiring acute therapy of any modality (i.e., surgical or external
             beam radiotherapy) within two weeks of enrollment or clinical instability, including
             signs or symptoms of brain edema. Subjects must demonstrate stable or decreasing brain
             metastasis by a noninvasive imaging scan and must be off steroids or on decreasing
             doses prior to enrollment.
          -  Treatment with another investigational drug product (therapeutic IND agents) within
             the last 30 days.
          -  Current abuse of alcohol or illicit drugs
          -  Existence of any medical or social issues likely to interfere with study conductor
             that may cause increased risk to the subject or to others, e.g., lack of ability to
             follow radiation safety precautions