Safety and preliminary efficacy results of 212 PbVMT-a-NET in advanced somatostatin receptor subtype 2 (SSTR2)-expressing neuroendocrine tumors (NETs).

635 Background: 212 PbVMT-a-NET is an alpha therapy agent targeting somatostatin receptor subtype 2 (SSTR2)-expressing tumors. Here, we report the results of a prospective, open-label, Phase I/IIa trial (NCT05636618), assessing safety, tolerability, pharmacokinetics, and preliminary efficacy of 212 PbVMT-a-NET in patients with advanced neuroendocrine tumors (NETs). Methods: Adults with well-differentiated unresectable or metastatic SSTR2-expressing NETs, who are peptide receptor radionuclide therapy (PRRT) naïve, and who progressed on at least one prior line of systemic therapy, are eligible. Participants can receive up to four cycles of 212 PbVMT-a-NET at the assigned dose level. Participants are followed for dose-limiting toxicity (DLT) observation up to 42 days after the first dose. Efficacy is evaluated by investigators according to RECIST criteria v1.1. Results: As of 16-Aug-2025 (data cut-off DCO) a total of 48 participants were enrolled into cohorts 1 and 2 and received at least one dose of 212 PbVMT-a-NET (n=2 in Cohort 1, and n=46 in Cohort 2 at a dose level of 92.5 MBq and 185 MBq, respectively). Among all participants treated with at least one dose of 212 PbVMT-a-NET (n=48), no DLTs, no grade 4 or 5 adverse events (AEs), and no treatment-related discontinuations, were observed. Median follow-up time was 28 weeks (range: 6-93). Nine participants were followed for DLT observation (n=2 in cohort 1 and n=7 in cohort 2).Seven of these patients were with no progression as of the DCO. Three out of the seven participants enrolled at the dose level of 185 MBq achieved a confirmed partial response (PR). Median follow-up time for participants included in the efficacy group was 72 weeks (range: 6-93). Cohort 3, at a dose level of 222 MBq, has recently been opened for enrollment. At the DCO, 4 participants were enrolled in this cohort. Updated safety outcome for all participants along with updated efficacy findings for participants in Cohort 1 and 2 with sufficient maturity, will be presented during the congress. Conclusions: 212 PbVMT-a-NET showed a favorable safety profile and promising clinical benefit for patients with advanced SSTR2-expressing NETs treated at the dose levels of 92.5 MBq and 185 MBq. The study is ongoing with Cohort 3 (222 MBq) currently open for enrollment. Clinical trial information: NCT05636618 .