Sanofi release data from a Phase II clinical trial for an investigational targeted alpha therapy (TAT), AlphaMedix (²¹²Pb-DOTAMTATE), as a treatment approach for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

The data was presented at the 2025 European Society for Medical Oncology (ESMO) Congress taking place from 17-21 October in Berlin, Germany. The results for AlphaMedix, showed clinical activity in patients with unresectable or metastatic GEP-NETs, including in those who were new to radioligand therapy and those whose disease had progressed after previous treatment.

Addressing an Unmet Need in GEP-NETs

GEP-NETs are a group of cancers that originate in the digestive tract and pancreas. While existing radioligand therapies (RLTs) that use beta radiation have become a treatment option, a need remains for patients who stop responding to these therapies.

Targeted Alpha Therapy is an approach that uses alpha particles, which emit energy over a very short distance. This method is designed to deliver radiation to cancer cells with a potential to limit exposure to surrounding tissue.

AlphaMedix is an investigational somatostatin receptor (SSTR) targeted alpha therapy (TAT) using the lead-212 isotope. Sanofi acquired the global commercial rights for AlphaMedix in licensing agreement with Orano Med and RadioMedix in September 2024.

Neuroendocrine tumors are a rare type of cancer, with a global prevalence estimated at 35 per 100,000 individuals. In the US, approximately 12,000 patients are diagnosed with neuroendocrine tumors annually. The five-year survival rate for patients with metastatic disease is approximately 60%.

Trial Design and Results

The ALPHAMEDIX-02 study (NCT05153772) was an open-label, multicenter Phase II trial evaluating the efficacy and safety of AlphaMedix in patients with advanced SSTR-positive GEP-NETs. The study included two groups: 35 patients who had not received prior RLT and 26 patients whose disease had progressed after prior beta-emitting RLT.

The primary efficacy endpoint for both groups was the Overall Response Rate (ORR). According to the presentations, the study met its primary efficacy endpoints. Secondary endpoints included progression-free survival and overall survival.

“The results observed in the ALPHAMEDIX-02 trial demonstrate levels of efficacy for a Targeted Alpha Therapy in both radioligand therapy-naïve and RLT-exposed populations,” said Dr. Ebrahim Delpassand, CEO of RadioMedix.

AlphaMedix demonstrated clinical activity in both patient cohorts. In the group of 35 patients who had not previously received any radioligand therapy (RLT-naïve), the treatment resulted in an objective response rate of 60% (57.1% as per independent assessment). Furthermore, a significant proportion of these patients, 94.3% (85.7% as per independent assessment), achieved disease control, which includes both tumor shrinkage and stable disease. The 36-month progression-free survival (PFS) for this group was reported at 72.3% (63.3% as per independent assessment).

For 26 patients who had already been treated with and progressed following a prior beta-emitting RLT (RLT-exposed), the therapy also showed activity. The objective response rate in this more heavily pre-treated cohort was 34.6% (19.2% as per independent assessment), with a disease control rate of 96.2%. The 18-month PFS for these RLT-exposed patients was 82.6% (88% as per independent assessment).

Safety and Tolerability Findings

The therapy demonstrated a similar safety profile in both patient cohorts. Within the RLT-naïve cohort, 85.7% of patients received all four doses of AlphaMedix, and 84.6% of patients within the RLT-exposed cohort.

All patients experienced at least one treatment-emergent adverse event. Grade 3 or higher adverse events were reported in 54.3% of RLT-naïve patients and 42.3% of RLT-exposed patients. A decrease in lymphocyte count was the most common Grade 3 or higher event in both groups.

“With AlphaMedix’s responses across both patient groups, the results indicate its potential in this cancer,” said Dr. Volker Wagner, Chief Medical Officer at Orano Med.

The Phase II data are expected to support further discussions with health authorities. AlphaMedix received Breakthrough Therapy Designation from the US Food and Drug Administration (FDA) in February 2024 for RLT-naïve patients with advanced GEP-NETs.

An international Phase III study is being planned. “This data could represent an advancement in how we treat gastroenteropancreatic neuroendocrine tumors,” said Dr. Christopher Corsico, Global Head of Development at Sanofi.