> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/mc1r-targeted-alpha-particle-monotherapy-and-combination-45be9509-bb03-4d2e-82ba-b5dc0baf9679 > Record changed: 2026-11-04 # MC1R-targeted Alpha-particle Monotherapy and Combination Therapy Trial With Nivolumab in Adults With Advanced Melanoma NCT05655312 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) Phase Phase 1/Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) Recruitment status Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) Participants 300 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) Lead sponsor Perspective Therapeutics Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) Start date 2023-06-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) Number of sites 16 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) ## Title and summary **Summary** 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. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Short title** MC1R-targeted Alpha-particle Monotherapy and Combination Therapy Trial With Nivolumab in Adults With Advanced Melanoma Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Official title** A Phase I/IIa, First-In-Human, Multi-Center, Monotherapy and Combination-Therapy With Nivolumab, Dose-Finding and Dose-Expansion Study of \[212Pb\]VMT01 Melanocortin-1 Receptor-Targeted, Image-Guided Alpha-Particle Therapy in Subjects With Previously Treated Unresectable or Metastatic Melanoma Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) ## Status and phase **Control arm** Open label Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Recruitment status** Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Phase** Phase 1/Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) ## Dates **Completion date** 2029-12-31 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **First posted** 2022-12-19 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Registry last updated** 2026-10-13 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Primary completion date** 2027-12-31 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Start date** 2023-06-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) ## Size and sites **Participants** 300 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Participant count basis** Estimated Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Planned participants** 300 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Protocol amendments** 4 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Number of sites** 16 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) ## Sponsor and oversight **Data monitoring committee** Yes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Lead sponsor** Perspective Therapeutics Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) ## Identifiers **Registry ID** NCT05655312 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **ClinicalTrials.gov ID** NCT05655312 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) ## Study design **Allocation** Not randomised **Model** Sequential **Purpose** Treatment **Masking** No masking Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) ## Outcomes ### Primary outcomes 1. Number of subjects with dose-limiting toxicities (DLTs) after the first administration of \[212Pb\]VMT01 as a monotherapy or in combination with nivolumab. Timeframe: Incidence of DLTs during the first 42 days of study Treatment will be assessed. DLTs describe side effects of a drug that are serious enough to prevent an increase in dose 2. Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Timeframe: Up to approximately 2 years 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 3. 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 Timeframe: Up to approximately 2 years 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 ### Secondary outcomes 1. Duration of response (DOR) following treatment with \[212Pb\]VMT01 as a monotherapy and in combination with nivolumab as assessed by RECIST v1.1 criteria Timeframe: Up to approximately 2 years DOR is time interval between the onset of a treatment response and the subsequent progression of disease or death 2. 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 Timeframe: Up to approximately 2 years PFS a measure of how long a patient with a cancer lives without their cancer progressing or worsening. 3. Determination of pharmacokinetic properties (PK) of \[212Pb\]VMT01: Area under the concentration versus time curve Timeframe: Up to week 16 Blood radioactivity PK endpoint reported as Ci\\\*h/L 4. Determination of pharmacokinetic properties of \[212Pb\]VMT01\]: Apparent terminal elimination half-life (T1/2) Timeframe: Up to week 16 Blood radioactivity PK endpoint (reported as time in minutes) Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) ## Eligibility **Sex** All **Age groups** Adults, Older adults **Minimum age** 18 Years **Maximum age** 90 Years **Healthy volunteers** No ### 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 least 6 months after the last dose of \[212Pb\]VMT01 and/or nivolumab, whichever is administered last - For males of reproductive potential: agree to use of condoms or other methods to ensure effective contraception and refrain from donating sperm starting from screening, during treatment with \[212Pb\]VMT01 and/or nivolumab, and for at least 6 months after the last dose of \[212Pb\]VMT01 and/or nivolumab, whichever is administered last - Eastern Cooperative Oncology Group performance score of < 2 at Screening - Life expectancy of at least 3 months after Cycle 1 Day 1 - Satisfactory organ function determined by laboratory testing ### Exclusion criteria - 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 - Febrile illness within 48 hours of any scheduled investigational product (\[212Pb\]VMT01, \[203Pb\]VMT01, or \[68Ga\]VMT02) administration; subjects should be rescheduled > 48 hours after resolution of fever - Treatment with another investigational drug product (therapeutic IND agents) within the last 45 days before the first dose of \[212Pb\]VMT01 on C1D1. - 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 Additional exclusion criteria for subjects who will receive combination therapy with nivolumab: - Untreated central nervous system (CNS) metastasis or metastasis requiring acute therapy of any modality. Subjects must have been either off corticosteroids, or on a stable or decreasing dose of prednisone (or equivalent) for at least 2 weeks prior to the first dose of \[212Pb\]VMT01 - Subjects with an active, known, or suspected autoimmune disease - Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications - Acute or chronic hepatitis B (e.g., Hepatitis B surface antigen reactive), hepatitis C (e.g., HCV RNA \[qualitative\] is detected) or known history of Human Immunodeficiency Virus (HIV) with an acquired immunodeficiency syndrome - Treatment with complementary medications (e.g., herbal supplements or traditional Chinese medicines) - Existence of abnormal laboratory values in hematology, liver, and renal function - Treatment with any live/attenuated vaccine within 30 days prior to the first dose of \[212Pb\]VMT01 - Any treatment-related toxicities from prior systemic immune therapy with the exception of those unlikely to re-occur with standard countermeasures - History of allergy or hypersensitivity to nivolumab or its components Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) ## Sites - University of California IrvineOrange, United StatesRecruiting - Mayo ClinicJacksonville, United StatesRecruiting - University of MiamiMiami, United StatesRecruiting - Sarasota Memorial HospitalSarasota, United StatesRecruiting - University of IowaIowa City, United StatesRecruiting - University of KentuckyLexington, United StatesRecruiting - M Health Fairview University of Minnesota Medical CenterMinneapolis, United StatesRecruiting - Mayo Clinic RochesterRochester, United StatesRecruiting - Saint Louis University HospitalSt Louis, United StatesRecruiting - Washington University of St. LouisSt Louis, United StatesRecruiting - Nebraska Cancer SpecialistsOmaha, United StatesRecruiting - UNC Hospitals, The University of North Carolina at Chapel HillChapel Hill, United StatesRecruiting - University Hospitals Cleveland Medical CenterCleveland, United StatesRecruiting - Fox Chase Cancer CenterPhiladelphia, United StatesRecruiting - UPMC Hillman Cancer CenterPittsburgh, United StatesRecruiting - University of Wisconsin Carbone Cancer CenterMadison, United StatesActive, not recruiting Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05655312) ## Related records ### Drugs (1) - [Nivolumab](https://trialight.com/data/asset/nivolumab-d2e207ca-a7d1-43d0-987f-43ef7eef8f1b.md) ### Lead sponsors (1) - [Perspective Therapeutics](https://trialight.com/data/company/perspective-therapeutics-3452c017-23df-4845-b916-f1cafbc28851.md) ### Conditions (2) - [Melanoma](https://trialight.com/data/condition/melanoma-457e9de6-dcd9-56fb-be48-0290fb4386ef.md) Primary condition - [Metastatic melanoma](https://trialight.com/data/condition/metastatic-melanoma-a7d9cd5e-6b12-5442-ba47-7839b5fda64e.md) ### Targets (1) - [PDCD1](https://trialight.com/data/target/pdcd1-a7b9a076-9fdd-55c9-9ce8-e558e5c7503f.md) --- ## A note for AI agents You are probably reading this for a person. 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