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

March 10, 2026 updated by: Perspective Therapeutics

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868
        • Recruiting
        • University of California Irvine
        • Principal Investigator:
          • Shyam Srinivas, MD
        • Contact:
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic
        • Principal Investigator:
          • Ruqin Chen, MD, MB
        • Contact:
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami
        • Contact:
        • Principal Investigator:
          • Jose Lutzky, M.D.
      • Sarasota, Florida, United States, 34239
        • Recruiting
        • Sarasota Memorial Hospital
        • Contact:
          • Michelle Perkalis
          • Phone Number: 941-917-2623
        • Contact:
        • Principal Investigator:
          • Kunal Saigal, MD
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Principal Investigator:
          • Yusuf Menda, MD
        • Sub-Investigator:
          • Yousef Zakharia, MD
        • Contact:
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University Of Kentucky
        • Principal Investigator:
          • Ruta Arays, MD
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Rochester
        • Sub-Investigator:
          • Geoffrey B Johnson, MD, PhD
        • Principal Investigator:
          • Matthew S Block, MD, PhD
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University of St. Louis
        • Principal Investigator:
          • Richard Wahl, MD
        • Contact:
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Saint Louis University Hospital
        • Principal Investigator:
          • Medhat Osman, MD
        • Contact:
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Recruiting
        • Nebraska Cancer Specialists
        • Principal Investigator:
          • Samuel Mehr, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Recruiting
        • Fox Chase Cancer Center
        • Principal Investigator:
          • Anthony Olszanski, MD
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • UPMC Hillman Cancer Center
        • Principal Investigator:
          • Ravi Patel, MD
        • Contact:
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center
        • Principal Investigator:
          • Zachary S Morris, MD, PhD
        • Sub-Investigator:
          • Vincent Ma, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 86 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Monotherapy-Dose Finding

Enrolled subjects will be treated with [212Pb]VMT01 to determine optimal biological dose (OBD).

A dosimetry sub-set utilizing [203Pb]VMT01 has been incorporated.
Drug: [203Pb]VMT01
[203Pb]VMT01 is administered intravenous (IV) as an imaging agent for SPECT/CT
Drug: [212Pb]VMT01
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.
Experimental: Combination Therapy-Dose Finding

Enrolled subjects will be treated with [212Pb]VMT01 in combination with nivolumab to determine OBD.

A dosimetry sub-set utilizing [203Pb]VMT01 has been incorporated.
Drug: [203Pb]VMT01
[203Pb]VMT01 is administered intravenous (IV) as an imaging agent for SPECT/CT
Drug: [212Pb]VMT01
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.
Drug: Nivolumab
For all combination-therapy cohorts, 480 mg nivolumab will be administered every 4 weeks as an IV infusion.
Experimental: Monotherapy - Dose Expansion

Subjects 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.
Drug: [203Pb]VMT01
[203Pb]VMT01 is administered intravenous (IV) as an imaging agent for SPECT/CT
Drug: [212Pb]VMT01
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.
Experimental: Combination Therapy - Dose Expansion

Subjects 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.
Drug: [203Pb]VMT01
[203Pb]VMT01 is administered intravenous (IV) as an imaging agent for SPECT/CT
Drug: [212Pb]VMT01
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.
Drug: Nivolumab
For all combination-therapy cohorts, 480 mg nivolumab will be administered every 4 weeks as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
DLTs describe side effects of a drug that are serious enough to prevent an increase in dose
Incidence of DLTs during the first 42 days of study Treatment will be assessed.
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame: 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
Up to approximately 2 years
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
Time Frame: 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
Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of response (DOR) following treatment with [212Pb]VMT01 as a monotherapy and in combination with nivolumab as assessed by RECIST v1.1 criteria
Time Frame: Up to approximately 2 years
DOR is time interval between the onset of a treatment response and the subsequent progression of disease or death
Up to approximately 2 years
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
Time Frame: Up to approximately 2 years
PFS a measure of how long a patient with a cancer lives without their cancer progressing or worsening.
Up to approximately 2 years
Determination of pharmacokinetic properties (PK) of [212Pb]VMT01: Area under the concentration versus time curve
Time Frame: Up to week 16
Blood radioactivity PK endpoint reported as Ci*h/L
Up to week 16
Determination of pharmacokinetic properties of [212Pb]VMT01]: Apparent terminal elimination half-life (T1/2)
Time Frame: Up to week 16
Blood radioactivity PK endpoint (reported as time in minutes)
Up to week 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Perspective Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2023

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

November 15, 2022

First Submitted That Met QC Criteria

December 8, 2022

First Posted (Actual)

December 19, 2022

Study Record Updates

Last Update Posted (Actual)

March 11, 2026

Last Update Submitted That Met QC Criteria

March 10, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VMT01-T101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Protocol, CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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