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Recurrent Melanoma (Skin)Phase 1/2NCT05655312

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

A Phase 1/2 study testing [203Pb]VMT01, [212Pb]VMT01 and Nivolumab in people with Recurrent Melanoma (Skin) and Metastatic Melanoma, run by Perspective Therapeutics at 16 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 90 years
What is being tested?
[203Pb]VMT01, [212Pb]VMT01 and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
16 sitesUnited States
Study dates
1 Jun 2023to 31 Dec 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

16 sites in 1 country. Contact the study team or a site near you to ask about taking part.

ClinicalTrials at Perspectivetherapeutics contact

206-676-0900

clinicaltrials@perspectivetherapeutics.com

16 sites in 1 country

United States16 sites, 15 recruiting

  • UNC Hospitals, The University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

    Doug Whelan, 919 - 966 - 4432, dwhelan@email.unc.edu

    Stergios Moschos, MD

    Recruiting

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

    Kathryn Bissler, 330-235-7425, Kathryn.Bissler@UHhospitals.org

    Ankit Mangla, MD

    Recruiting

  • University of Iowa

    Iowa City, Iowa, 52242

    Kellie Bodeker, RN, BSN, (319) 384-9425, kellie-bodeker@uiowa.edu

    Yusuf Menda, MD

    Recruiting

  • Mayo Clinic

    Jacksonville, Florida, 32224

    Taylor Yates, 904-953-3007, yates.taylor@mayo.edu

    Ruqin Chen, MD, MB

    Recruiting

  • University of Kentucky

    Lexington, Kentucky, 40536

    Benton Patrick, 859-323-6237, Benton.Patrick@uky.edu

    Ruta Arays, MD

    Recruiting

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

    Active, not recruiting

  • University of Miami

    Miami, Florida, 33136

    Sandel Cepero, 305-243-6855, s.cepero@miami.edu

    Jose Lutzky, M.D.

    Recruiting

  • M Health Fairview University of Minnesota Medical Center

    Minneapolis, Minnesota, 55455

    Jinan Ali, 612-624-9071, alixx779@umn.edu

    Benjamin Manning, MD

    Recruiting

  • Nebraska Cancer Specialists

    Omaha, Nebraska, 68130

    Marlene Bridwell, 402-691-5252, mbridwell@nebraskacancer.com

    Samuel Mehr, MD

    Recruiting

  • University of California Irvine

    Orange, California, 92868

    Research Study Line, 877-827-8839, ucstudy@uci.edu

    Shyam Srinivas, MD

    Recruiting

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

    Hue Nice, 215-728-4325, Hue.Nice@fccc.edu

    Anthony Olszanski, MD

    Recruiting

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

    Eunice Acampado, 412-623-1322, acampadoem@upmc.edu

    Ravi Patel, MD

    Recruiting

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

    Alisha Birgin, 507-266-9955, Birgin.Alisha@mayo.edu

    Matthew S Block, MD, PhD

    Recruiting

  • Sarasota Memorial Hospital

    Sarasota, Florida, 34239

    Michelle Perkalis, 941-917-2623

    michelle-perkalis@smh.com

    Recruiting

  • Saint Louis University Hospital

    St Louis, Missouri, 63110

    Chelsea Webb, 314-617-2899, chelsea.may@health.slu.edu

    Medhat Osman, MD

    Recruiting

  • Washington University of St. Louis

    St Louis, Missouri, 63110

    Mahsa Ghajarzadeh, gmahsa@wustl.edu

    Richard Wahl, MD

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

This is a prospective, multi-center open-label dose-finding, dose-expansion study of [212Pb]VMT01 as a monotherapy or in combination with nivolumab in up to 300 subjects with histologically confirmed melanoma and a positive MC1R imaging scan with imaging agents [203Pb]VMT01 or [68Ga]VMT02.

MC1R is a receptor that is expressed on the surface of melanoma cells and therefore is an attractive therapeutic target for melanoma treatment. Lead-212 ([212Pb]-) based peptide-radiopharmaceuticals are an emerging class of targeted alpha-particle cancer therapies that have potential to improve delivery of a highly effective form of radiation.

This study will be conducted in 3 parts:

Part 1: Monotherapy Dose-Finding

Part 2: Combination-Therapy Dose-Finding

Part 3: Dose Expansion

Enrolled subjects in Monotherapy may receive up to 3 doses of [212Pb]VMT01 approximately 8 weeks apart and subjects in combination therapy may receive up to 3 doses of [212Pb]VMT01 along with nivolumab. Nivolumab will be administered every 4 weeks for up to 24 months.

A Dosimetry sub-set utilizing an imaging surrogate, [203Pb]VMT01, has been incorporated into the study in order to assess organ biodistribution and tumor uptake of the investigational products. This study will also estimate radiation dosimetry and correlate uptake of the investigation products with observed toxicities and efficacy.

Being tested
[203Pb]VMT01, [212Pb]VMT01, Nivolumab
Keywords
Melanoma, Theranostic, Radiopharmaceutical, Radiotherapy, Alpha Particle, Melanocortin Receptor Sub-type 1 (MC1R), VMT01-T101, Pb-203, Pb-212, Ga-68, Nivolumab
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • [203Pb]VMT01Drug

    [203Pb]VMT01 is administered intravenous (IV) as an imaging agent for SPECT/CT

  • [212Pb]VMT01Drug

    Subjects 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.

  • NivolumabDrug

    For all combination-therapy cohorts, 480 mg nivolumab will be administered every 4 weeks as an IV infusion.

Study groups in NCT05655312
Study groupRoleWhat they receive
Monotherapy-Dose FindingExperimentalEnrolled subjects will be treated with [212Pb]VMT01 to determine optimal biological dose (OBD). A dosimetry sub-set utilizing [203Pb]VMT01 has been incorporated.
Receives: Drug: [203Pb]VMT01; Drug: [212Pb]VMT01
Combination Therapy-Dose FindingExperimentalEnrolled subjects will be treated with [212Pb]VMT01 in combination with nivolumab to determine OBD. A dosimetry sub-set utilizing [203Pb]VMT01 has been incorporated.
Receives: Drug: [203Pb]VMT01; Drug: [212Pb]VMT01; Drug: Nivolumab
Monotherapy - Dose ExpansionExperimentalSubjects will be enrolled at previously identified recommended phase 2 dose (RP2D) for confirmation of the RP2D and regimen for the Phase 2 dose-expansion cohort. A dosimetry sub-set utilizing [203Pb]VMT01 has been incorporated.
Receives: Drug: [203Pb]VMT01; Drug: [212Pb]VMT01
Combination Therapy - Dose ExpansionExperimentalSubjects will be enrolled at previously identified RP2D for its confirmation and verification of regimen for the Phase 2 dose-expansion cohort. A dosimetry sub-set utilizing [203Pb]VMT01 has been incorporated.
Receives: Drug: [203Pb]VMT01; Drug: [212Pb]VMT01; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Incidence of DLTs during the first 42 days of study Treatment will be assessed.

  2. 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

    Measured: Up to approximately 2 years

  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

    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

    Measured: Up to approximately 2 years

Secondary outcomes (4)

  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

    DOR is time interval between the onset of a treatment response and the subsequent progression of disease or death

    Measured: Up to approximately 2 years

  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

    PFS a measure of how long a patient with a cancer lives without their cancer progressing or worsening.

    Measured: Up to approximately 2 years

  3. Determination of pharmacokinetic properties (PK) of [212Pb]VMT01: Area under the concentration versus time curve

    Blood radioactivity PK endpoint reported as Ci*h/L

    Measured: Up to week 16

  4. Determination of pharmacokinetic properties of [212Pb]VMT01]: Apparent terminal elimination half-life (T1/2)

    Blood radioactivity PK endpoint (reported as time in minutes)

    Measured: Up to week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2022
  2. Study start1 Jun 2023
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Phase I/IIa First-in-Human Study of \[212Pb\]VMT01 Targeted Alpha-Particle Therapy for MC1R Positive Advanced Malignant Melanoma
Masking
None (open label)
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05655312
Sponsor's protocol ID
VMT01-T101
Status last verified
Oct 2026
First submitted
15 Nov 2022
Last updated
13 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: Protocol, CSR

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing [203Pb]VMT01, [212Pb]VMT01 and Nivolumab in people with Recurrent Melanoma (Skin) and Metastatic Melanoma, run by Perspective Therapeutics at 16 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact ClinicalTrials at Perspectivetherapeutics (206-676-0900, clinicaltrials@perspectivetherapeutics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of subjects with dose-limiting toxicities (DLTs) after the first administration of [212Pb]VMT01 as a monotherapy or in combination with nivolumab. (time frame: Incidence of DLTs during the first 42 days of study Treatment will be assessed.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05655312.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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