MC1R-targeted Alpha-particle Monotherapy and Combination Therapy Trial With Nivolumab in Adults With Advanced Melanoma
NCT ID: NCT05655312
Last Updated: 2026-01-16
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
300 participants
INTERVENTIONAL
2023-06-01
2029-12-31
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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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.
[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.
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.
[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.
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.
[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.
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.
[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.
Interventions
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[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.
Eligibility Criteria
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Inclusion Criteria
* 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
* 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
* 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
18 Years
90 Years
ALL
No
Sponsors
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Perspective Therapeutics
INDUSTRY
Responsible Party
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Locations
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University of California Irvine
Orange, California, United States
University of Miami
Miami, Florida, United States
Sarasota Memorial Hospital
Sarasota, Florida, United States
University of Iowa
Iowa City, Iowa, United States
University of Kentucky
Lexington, Kentucky, United States
Mayo Clinic Rochester
Rochester, Minnesota, United States
Saint Louis University Hospital
St Louis, Missouri, United States
Washington University of St. Louis
St Louis, Missouri, United States
Nebraska Cancer Specialists
Omaha, Nebraska, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States
Countries
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Central Contacts
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Facility Contacts
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Michelle Perkalis
Role: primary
Role: backup
Other Identifiers
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VMT01-T101
Identifier Type: -
Identifier Source: org_study_id
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