212Pb-DOTAMTATE: Impressive Efficacy in Treatment-Naive and Refractory Cohorts

In an interview with Targeted Oncology at the 2025 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium, Jonathan Strosberg, MD, professor at Moffitt Cancer Center, explains the objectives and key design features of the phase 2 ALPHAMEDIX-02 trial (NCT05153772) and showcases key efficacy data for both treatment-naive and treatment-refractory cohorts.

Read the full interview here.

The phase 2 trial is evaluating the efficacy and safety of ²¹²Pb-DOTAMTATE (AlphaMedix), an investigational targeted alpha particle radioligand therapy, in patients with SSTR-expressing, unresectable or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The study was designed with 2 distinct cohorts: those who were peptide receptor radionuclide therapy (PRRT)-naive and those who had received prior lutetium-based PRRT. The primary end points measured include investigator-assessed overall response rate (ORR) and adverse events (AEs), while secondary end points included progression-free survival (PFS) and overall survival (OS).

The efficacy outcomes for both cohorts were reported as quite favorable and “impressive” by Dr Strosberg. A 60% ORR was observed in the PRRT-naive cohort (n = 35), with most of the remaining patients achieving stable disease as their best outcome. Long-term survival data was also strong, with a 36-month PFS rate reaching approximately 70% to 75% and 36-month OS rate at approximately 88%.

Dr Strosberg noted that the PRRT-refractory cohort, a heavily pretreated population, was smaller (n = 26) and had a shorter follow-up time of about 14.5 months, having been enrolled later in the study. Given heavy pretreatment, this group had a lower ORR (35%) compared with the PRRT-naive cohort, but the level of response activity was still considered strong for this population. The 18-month PFS rate ranged from approximately 75% to 80%.

While impressive efficacy was seen in both cohorts, Dr Strosberg reiterates the importance of a randomized study to confirm these positive treatment effects, as well as the need to investigate some long-term toxicities associated with treatment, on which he elaborates in the subsequent segment.