RECRUITING

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

Conditions

Melanoma (Skin)Metastatic Melanoma Melanoma Stage IV Mucosal Melanoma Melanoma Stage III Melanoma Theranostic Radiopharmaceutical Radiotherapy Alpha Particle Melanocortin Receptor Sub-type 1 (MC1R)VMT01-T101 Pb-203 Pb-212 Ga-68 Nivolumab

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase I/IIa, First-In-Human, Multi-Center, Monotherapy and Combination-Therapy With Nivolumab, Dose-Escalation 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

Quick Facts

Study Start:2023-06-01

Study Completion:2029-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05655312

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.

Ages Eligible for Study:18 Years to 90 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 melanoma * Previously progressed (clinical or radiological progression) on at least one approved first-line therapy for metastatic 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 30 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	* 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 * Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years 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

Inclusion Criteria

Exclusion 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 melanoma
* Previously progressed (clinical or radiological progression) on at least one approved first-line therapy for metastatic 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 30 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

* 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
* Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years 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

Contacts and Locations

Study Contact

Markus Puhlmann, MD

CONTACT

319-665-2151

mpuhlmann@perspectivetherapeutics.com

Study Locations (Sites)

Biogenix Molecular

Miami, Florida, 33165

United States

University of Iowa

Iowa City, Iowa, 52242

United States

University of Kentucky

Lexington, Kentucky, 40536

United States

Mayo Clinic Rochester

Rochester, Minnesota, 55905

United States

Saint Louis University Hospital

Saint Louis, Missouri, 63110

United States

Washington University of St. Louis

Saint Louis, Missouri, 63110

United States

Nebraska Cancer Specialists

Omaha, Nebraska, 68130

United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

United States

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

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 Registration Dates

Study Start Date2023-06-01

Study Completion Date2029-12-31

Study Record Updates

Study Start Date2023-06-01

Study Completion Date2029-12-31

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Melanoma (Skin)
Metastatic Melanoma
Melanoma Stage IV
Mucosal Melanoma
Melanoma Stage III