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A phase I/IIa, first-in-human, multicenter, monotherapy and combination therapy with nivolumab dose-finding study of [212Pb]VMT01 melanocortin-1-receptor-targeted, image-guided, alpha-particle therapy in subjects with previously treated unresectable or metastatic melanoma
Abstract   Open access   Peer reviewed

A phase I/IIa, first-in-human, multicenter, monotherapy and combination therapy with nivolumab dose-finding study of [212Pb]VMT01 melanocortin-1-receptor-targeted, image-guided, alpha-particle therapy in subjects with previously treated unresectable or metastatic melanoma

Zachary Scott Morris, Richard L. Wahl, Jose Lutzky, Ravi Patel, Samuel Mehr, Anthony J. Olszanski, Yusuf Menda, Ruta Arays, Shyam M. Srinivas, Kunal Saigal, …
Journal of clinical oncology, Vol.44(16_suppl), pp.9525-9525
06/01/2026
DOI: 10.1200/JCO.2026.44.16_suppl.9525
url
https://doi.org/10.1200/JCO.2026.44.16_suppl.9525View
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Abstract

9525Background: Melanocortin-1 receptor (MC1R) is a novel target for radiopharmaceutical therapy and is highly expressed on melanoma tumor cells. VMT01 is an MC1R-targeted peptide.203Pb is used for patient selection via SPECT imaging. Peptide radiolabeling with 212Pb delivers alpha-particle therapy. Here, we present data on the treatment of adult patients with MC1R-positive metastatic melanoma receiving [212Pb]VMT01 either as a monotherapy or in combination with the programmed death-1 (PD-1) checkpoint inhibitor, nivolumab. Methods: This is an ongoing phase I/IIa, first-in-human, prospective, multicenter, open-label, radioactive dose-finding and dose-expansion trial. The objectives are to investigate safety, pharmacokinetics, dosimetry, and efficacy. Participants receive up to 3 treatment cycles with either [212Pb]VMT01 3 mCi, 5 mCi, or 1.5 mCi monotherapy, or combination therapy with [212Pb]VMT01 (1.5 mCi) + nivolumab (480 mg, Q4W) or [212Pb]VMT01 (3 mCi) + nivolumab. Participants are evaluated for any DLTs for the first 6 weeks after cycle 1. Efficacy is assessed by RECIST v1.1 criteria by the investigator. Results: As of 24 December 2025, 26 participants (53.8% male; median age: 68 years [range: 27-81]) with MC1R-positive metastatic melanoma were enrolled. The median prior systemic therapies was 4. All 26 enrolled participants received ≥1 dose of [²¹²Pb]VMT01. No DLTs were reported. All SAEs (including one grade 5 SAE) were attributed to disease progression. Most TEAEs were grade 1 (19.2%) and grade 2 (34.6%). Grade 3 TEAEs occurred in 8 participants (30.8%), 5 on monotherapy and 3 on combination therapy (3 mCi + nivolumab). Of the 22 evaluable participants, 1 PR, 9 SD, and 12 PD were reported. Four participants had progression-free survival of ≥6 months. Conclusions: [212Pb]VMT01 as a monotherapy and in combination with nivolumab was generally safe and well-tolerated in 26 enrolled participants, with antitumor activity observed at the 3 mCi dose level. These data may be supplemented with a more complete follow-up at the time of the meeting. Clinical trial information: NCT05655312.

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