Alpha-emitting radiopharmaceutical therapy with 212Pb-DOTAMTATE demonstrated frequent, durable responses and a favorable safety profile in patients with peptide receptor radionuclide therapy (PRRT)–naïve, somatostatin receptor (SSTR)–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to updated 2-year results from the phase 2 ALPHAMEDIX 02 study.

These findings were presented at the NANETs 2025 Multidisciplinary NET Medical Symposium.

The investigational agent, 212Pb-DOTAMTATE, delivers alpha radiation via targeted SSTR binding, inducing potent double-stranded DNA breaks with minimal collateral damage to surrounding tissue. This targeted, high–linear energy transfer mechanism distinguishes it from established beta-emitting therapies such as lutetium-177–based PRRT.

In the ongoing multicenter, open-label study, 35 PRRT-naïve patients with unresectable or metastatic, SSTR-positive GEP-NETs received 212Pb-DOTAMTATE at 67.6 μCi/kg every 8 weeks for up to 4 cycles. Most patients (89%) had well-differentiated grade 1 or 2 disease, and the most common primary tumor sites were the pancreas and small intestine (43% each).

The primary study end points were overall response rate (ORR) per RECIST1.1, and incidence and severity of adverse events (AEs). Secondary end points included progression free survival (PFS) and overall survival (OS).

Among evaluable patients, 20 of 35 achieved confirmed partial responses, corresponding to an ORR of 57.1% (95% confidence interval [CI], 39.4 to 73.7). An additional 37.1% achieved stable disease, for a disease control rate exceeding 90%. Fourteen of 20 responders (70%) maintained responses ≥12 months, and 2 patients sustained responses ≥24 months, underscoring the therapy’s durability. At 2 years, PFS and OS rates were 71.3% and 88.2%, respectively, reflecting strong long-term outcomes.

Treatment was well tolerated. All patients experienced at least 1 treatment-emergent adverse event (TEAE), and the most frequent grade 3 to 4 event was lymphopenia (25.7%). No new safety signals were identified with longer follow-up, and hematologic toxicity was consistent with expectations for radiopharmaceutical therapy.

These findings suggest that 212Pb-DOTAMTATE delivers potent, durable antitumor activity in patients with advanced SSTR-positive GEP-NETs who have not received prior PRRT. As the field moves toward personalized radionuclide therapy, this alpha-emitting approach may represent an important advancement beyond beta-based agents for patients with well-differentiated neuroendocrine tumors.

Source:

Strosberg JR, Naqvi S, Cohn AL, et al. Long-term Follow-up of PRRT-Naïve Patients with GEPNETs Treated with Targeted Alpha Therapy 212PbDOTAMTATE in the Phase 2 ALPHAMEDIX 02 Trial. Presented at the NANETs 2025 Multidisciplinary NET Medical Symposium; October 23-25, 2025. Austin, Texas. Abstract ID 33414