Recruiting
Phase 1
Phase 2

Alpha-Particle & Nivolumab

Sponsor:

Perspective Therapeutics

Code:

NCT05655312

Conditions

Recurrent Melanoma (Skin)

Metastatic Melanoma

Melanoma Stage IV

Melanoma Stage III

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

[203Pb]VMT01

[212Pb]VMT01

Nivolumab

Study Details

Brief 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.

Conditions

Recurrent Melanoma (Skin)

Metastatic Melanoma

Melanoma Stage IV

Melanoma Stage III

Study ID

NCT05655312

Start date

Jun 1, 2023

Status verified date

Jun, 2026

Completion date

Dec 31, 2029

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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 Design

Enrollment

300 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

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.

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.

Interventions

[203Pb]VMT01

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

[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.

Nivolumab

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

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. ]
  • Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: 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 ]

Central Contacts and Locations

Central contacts

ClinicalTrials at Perspectivetherapeutics

206-676-0900clinicaltrials@perspectivetherapeutics.com

Locations

University of California Irvine

Recruiting

Orange, California, United States, 92868

Contacts

Research Study Line

877-827-8839ucstudy@uci.edu

Principal Investigator:

Shyam Srinivas, MD

Mayo Clinic

Recruiting

Jacksonville, Florida, United States, 32224

Contacts

Taylor Yates

904-953-3007yates.taylor@mayo.edu

Principal Investigator:

Ruqin Chen, MD, MB

University of Miami

Recruiting

Miami, Florida, United States, 33136

Contacts

Sandel Cepero

305-243-6855s.cepero@miami.edu

Principal Investigator:

Jose Lutzky, M.D.

Sarasota Memorial Hospital

Recruiting

Sarasota, Florida, United States, 34239

Contacts

Michelle Perkalis

941-917-2623

michelle-perkalis@smh.com

Principal Investigator:

Kunal Saigal, MD

University of Iowa

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Kellie Bodeker, RN, BSN

319-384-9425kellie-bodeker@uiowa.edu

Principal Investigator:

Yusuf Menda, MD

University of Kentucky

Recruiting

Lexington, Kentucky, United States, 40536

Contacts

Benton Patrick

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

Principal Investigator:

Ruta Arays, MD

Mayo Clinic Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Alisha Birgin

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

Principal Investigator:

Matthew S Block, MD, PhD

Saint Louis University Hospital

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Chelsea Webb

314-617-2899chelsea.may@health.slu.edu

Principal Investigator:

Medhat Osman, MD

Washington University of St. Louis

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Mahsa Ghajarzadeh

gmahsa@wustl.edu

Principal Investigator:

Richard Wahl, MD

Nebraska Cancer Specialists

Recruiting

Omaha, Nebraska, United States, 68130

Contacts

Marlene Bridwell

402-691-5252mbridwell@nebraskacancer.com

Principal Investigator:

Samuel Mehr, MD

Fox Chase Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19111

Contacts

Hue Nice

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

Principal Investigator:

Anthony Olszanski, MD

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Eunice Acampado

412-623-1322acampadoem@upmc.edu

Principal Investigator:

Ravi Patel, MD

More Information

Sponsor

Perspective Therapeutics

Last update posted

Jun 10, 2026

Last verified

Jun, 2026

Keywords

  • Melanoma
  • Theranostic
  • Radiopharmaceutical
  • Radiotherapy
  • Alpha Particle
  • Melanocortin Receptor Sub-type 1 (MC1R)
  • VMT01-T101
  • Pb-203
  • Pb-212
  • Ga-68
  • Nivolumab

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Perspective Therapeutics on 2026-06-10.