NCT05655312

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

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 300 (estimated)
• Sponsor: Perspective Therapeutics · Industry
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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 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

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

Interventions

Type	Name	Description
DRUG	[203Pb]VMT01	\[203Pb\]VMT01 is administered intravenous (IV) as an imaging agent for SPECT/CT
DRUG	[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.
DRUG	Nivolumab	For all combination-therapy cohorts, 480 mg nivolumab will be administered every 4 weeks as an IV infusion.

Timeline

• Start date: 2023-06-01
• Primary completion: 2027-12-31
• Completion: 2029-12-31
• First posted: 2022-12-19
• Last updated: 2026-03-11

Locations

13 sites across 1 country: United States

Regulatory

• FDA-regulated drug study