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

Perspective Therapeutics17 个研究点分布在 1 个国家目标入组 300 人开始时间: 2023年6月1日最近更新: 2026年6月10日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方: Perspective Therapeutics
入组人数: 300
试验地点: 17
主要终点: Number of subjects with dose-limiting toxicities (DLTs) after the first administration of [212Pb]VMT01 as a monotherapy or in combination with nivolumab.

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

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.

详细描述

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

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Sequential
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 90 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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]VMT
•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

排除标准

•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 C1D
•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