Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy

Study Overview
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Brief Summary
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The study hypothesis is that new imaging agents [203Pb]VMT01 and [68Ga]VMT02 can be safely used in humans without independent biological effect and can be used to image melanoma tumors expressing the melanocortin sub-type 1 receptor (MC1R) by SPECT/CT and PET/CT imaging modalities respectively.

Detailed Description
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This is a first-in-human study evaluating the suitability of [203Pb]VMT01 for SPECT/CT imaging and [68Ga]VMT02 for PET/CT imaging of MC1R-expressing metastatic melanoma. Study results will provide foundational data to develop imaging and dosing for future therapeutic trials of [212Pb]VMT01 for the treatment of metastatic melanoma. The study will be a cross-over study with the participants serving as their own comparator. Participants with positive FDG-PET scans for stage IV (or inoperable stage III) metastatic melanoma will undergo SPECT/CT scans utilizing [203Pb]VMT01 followed a few weeks later by PET/CT scans utilizing [68Ga]VMT02, or vice versa. The order of the imaging agents will be randomly assigned.

Official Title
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A Phase 1 Cross-over Biodistribution Study of [203Pb]VMT01 for Single Photon Emission Computed Tomography (SPECT) Imaging and [68Ga]VMT02 for Positron Emission Tomography (PET) Imaging of Stage IV Metastatic Melanoma

Conditions
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Melanoma Stage IV, Melanoma, Uveal, Melanoma, Mucosal, Melanoma (Skin)

Intervention / Treatment
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* Drug: [203Pb]VMT01
* Drug: [68Ga]VMT02


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with Stage IV metastatic melanoma, or inoperable Stage III equivalent Baseline fluorodeoxyglucose (FDG)-PET scan available from within 30 days prior to date of enrollment Blood counts and metabolic results within protocol limits within 14 days prior to enrollment Ability to lie flat and still for a minimum of two hours for imaging Male and female participants with reproductive potential must agree to use highly effective contraception in preparation of the study, during the study, and for 4 weeks following the last dose of an investigative imaging agent Documented life expectancy of at least 3 months Exclusion Criteria: Active secondary malignancy Prior treatment (for any reason) with radioactive nuclides; imaging tracers are acceptable Pregnancy or breast feeding a child Uncontrolled infection Treatment with another investigational drug within 30 days prior to enrollment date Any treatment with BRAF inhibitors since the baseline FDG-PET scan or plans for such treatment during the study Kidney function not within protocol limits BMI>40 kg/m2 History of a condition resulting in anaphylaxis or angioedema

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: [203Pb]VMT01 first<br>Participants randomized to this arm will receive imaging agent [203Pb]VMT01 and undergo SPECT/CT imaging first. Later, participants in this arm will receive [68Ga]VMT02 and undergo PET/CT imaging. | Drug: [203Pb]VMT01<br>* Diagnostic imaging radiopharmaceutical; by intravenous infusion<br>Drug: [68Ga]VMT02<br>* Diagnostic imaging radiopharmaceutical; by intravenous infusion<br>|
| Active Comparator: [68Ga]VMT02 first<br>Participants randomized to this arm will receive imaging agent [68Ga]VMT02 and undergo PET/CT imaging first. Later, participants in this arm will receive [203Pb]VMT01 and undergo SPECT/CT imaging. | Drug: [203Pb]VMT01<br>* Diagnostic imaging radiopharmaceutical; by intravenous infusion<br>Drug: [68Ga]VMT02<br>* Diagnostic imaging radiopharmaceutical; by intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Study Imaging Agent-Associated Adverse Events (AE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Adverse Events (AEs) will be assessed for severity according to CTCAE v5.0 and for relatedness to each of the investigative imaging agents ([203Pb]VMT01 and [68Ga]VMT02). Assessments attributed as possibly, probably, or definitely related to the imaging agent will be considered related. | Visit 1 (Day 1) through Visit 5 (approximately Day 60 but could extend up to Day 108); ongoing Serious Adverse Events (SAE) will be followed for no longer than Day 65 or 30 days from the date of the SAE report (whichever is later). | 
| Biodistribution of [68Ga]VMT02 | Biodistribution will be calculated by utilizing PET/CT scans. | 12 hours | 
| Biodistribution of [203Pb]VMT01 | Biodistribution will be calculated by utilizing SPECT/CT scans. | 24 hours | 
| Peak Plasma Concentration (Cmax) of [203Pb]VMT01 | Cmax will be determined by blood sampling and direct radioactivity measurements. | 24 hours | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) for [203Pb]VMT01 | AUC will be determined by blood sampling and direct radioactivity measurements. | 24 hours | 
| Renal Excretion of [203Pb]VMT01 | Renal excretion will be determined by urine sampling and direct radioactivity measurements. | 24 hours | 
| Modeling of [203Pb]VMT01 Dosimetry | Dosimetry will be modeled by utilizing the SPECT/CT scans. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MC1R Expression Correlation Between Archived Tumor Tissue and Study Imaging | Archived (previously collected) tumor tissue will be tested for MC1R expression and compared to study images obtained using MC1R targeted imaging agents, [203Pb]VMT01 and [68Ga]VMT02. The data will be assessed for an association between positive tissue and positive images. | Historical tissue sample (collected <365 days before study enrollment) compared to Visit 1 (Day 1) and Visit 3 (Day 21-34) imaging | 
| Cancer Site Correlation Between Standard of Care Imaging Compared to Study Imaging | Sites of cancer detected previously by imaging will be compared to the presence or absence of positive imaging scans with the study agents, [203Pb]VMT01 and [68Ga]VMT02. | Historical imaging information compared to Visit 1 (Day 1) and Visit 3 (Day 21-34) imaging | 
| Dosimetry will be Calculated for each Study Imaging Agent by Measuring the Cumulative Absorbed Dose of Radiation to the Participant's Individual Organs and Tumors | For a given participant, dosimetry calculations will be compared between the two imaging agents with respect to cumulative absorbed dose of radiation. | Visit 1 (Day 1) and Visit 3 (Day 21-34) imaging | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VMT01, Melanoma, Theranostic, Radiopharmaceutical, Radiotherapy, Alpha-Particle, Diagnostic, Metastatic, Single Photon Emission Computed Tomography (SPECT), Positron Emission Tomography (PET), Melanocortin Receptor Sub-type 1 (MC1R), VMT02, Pb-203, Ga-68, Cancer, Immunohistochemistry (IHC)