[212Pb]VMT-α-NET Targeted Alpha-Particle Therapy (TAT) For Advanced Somatostatin Receptor 2-Positive (SSTR2+) Neuroendocrine Tumours (NETs): Mature Safety and Preliminary Efficacy For Enrollment From Dose-Finding Cohorts 1 and 2 (n=44)T

Document Type

Conference Proceeding

Publication Date

9-2025

Publication Title

Annals of Oncology

Abstract

Background: [ 212Pb]VMT-α-NET is a novel, next-generation TAT designed to optimize biodistribution and therapeutic index. Data are reported from the dose-finding phase 1/2a clinical trial [NCT05636618]. Methods: Treatment of patients (pts) with SSTR2+ NETs with [ 212Pb]VMT-α-NET was investigated for safety, PK/dosimetry, and efficacy. Peptide receptor radionuclide therapy naïve pts with progressive disease following ≥ 1 prior line of systemic therapy were treated with up to four doses of study therapy. Dose-finding proceeded using the Bayesian modified toxicity probability interval 2 (mTPI-2) design where 2 pts were treated at dose level 1 with 92.5 MBq (2.5 mCi) of administered activity per dose, and 7 pts were treated at dose level 2 with 185 MBq (5 mCi) / dose for dose-limiting toxicity observation. As of 7-May-2025, 35 additional pts were enrolled into cohort 2 to more fully characterize safety and efficacy. Results: The first 9 cohort 1 and 2 pts, all with gastroenteropancreatic NETs, were treated and followed for at least 1.5 years prior to 17-Oct-2025. Among these pts, at the time of abstract submission, no DLTs or grade ≥4 adverse events (AEs) were observed, and there was no dysphagia or high-grade renal injury. Side effects that were observed, including haematologic AEs, were infrequent and low grade. Four (4) of the 7 pts in cohort 2 achieved an investigator-assessed RECIST v1.1 partial response. Three (3) responses were confirmed; 1 was pending confirmation. Of the 35 additional cohort 2 pts, no DLTs, high grade AEs, dysphagia or high-grade renal injury were observed at the time of abstract submission. Safety for all and efficacy for a mature subgroup will be reported at the congress. Conclusions: [ 212Pb]VMT-α-NET is a well-tolerated, novel, next-generation TAT that demonstrates noteworthy clinical activity at the 185 MBq (5 mCi) dose level. These data justify further clinical development of this promising therapy.

Volume

36

Issue

S2

First Page

S630

Comments

European Society for Medical Oncology (ESMO) Congress 2025, October 17-21, 2025, Berlin, Germany

Last Page

S630

DOI

10.1016/j.annonc.2025.08.1602

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