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

NCT05655312 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: VMT01-T101
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 13

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

Metastatic Melanoma; Melanoma Stage IV; Melanoma Stage III; Recurrent Melanoma (Skin)

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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

  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

  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

  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 Outcomes (4)

• Duration of response (DOR) following treatment with [212Pb]VMT01 as a monotherapy and in combination with nivolumab as assessed by RECIST v1.1 criteria

  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

  Up to approximately 2 years

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

  Up to week 16

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

  Up to week 16

Study Arms (4)

Monotherapy-Dose Finding

EXPERIMENTAL

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; Drug: [212Pb]VMT01

Combination Therapy-Dose Finding

EXPERIMENTAL

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; Drug: [212Pb]VMT01; Drug: Nivolumab

Monotherapy - Dose Expansion

EXPERIMENTAL

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; Drug: [212Pb]VMT01

Combination Therapy - Dose Expansion

EXPERIMENTAL

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; Drug: [212Pb]VMT01; Drug: Nivolumab

Interventions

[212Pb]VMT01 DRUG

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.

Combination Therapy - Dose Expansion; Combination Therapy-Dose Finding; Monotherapy - Dose Expansion; Monotherapy-Dose Finding

Nivolumab DRUG

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

Combination Therapy - Dose Expansion; Combination Therapy-Dose Finding

[203Pb]VMT01 DRUG

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

Combination Therapy - Dose Expansion; Combination Therapy-Dose Finding; Monotherapy - Dose Expansion; Monotherapy-Dose Finding

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Perspective Therapeutics: lead

Study Sites (13)

University of California Irvine

Orange, California, 92868, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Sarasota Memorial Hospital

Sarasota, Florida, 34239, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

University of Kentucky

Lexington, Kentucky, 40536, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Saint Louis University Hospital

St Louis, Missouri, 63110, United States

RECRUITING

Washington University of St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

ClinicalTrials at Perspectivetherapeutics

CONTACT

206-676-0900; clinicaltrials@perspectivetherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase I/IIa First-in-Human Study of \[212Pb\]VMT01 Targeted Alpha-Particle Therapy for MC1R Positive Advanced Malignant Melanoma

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: December 19, 2022
• Study Start: June 1, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

US (13)