Positive results from the ALPHAMEDIX-02 phase 2 study showed AlphaMedix (212Pb-DOTAMTATE), an investigational somatostatin receptor-targeted alpha therapy using the lead-212 isotope, met all primary efficacy endpoints and demonstrated clinically meaningful overall response rates and prolonged clinical benefits in both peptide receptor radionuclide therapy (PRRT)-naïve and PRRT-exposed patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
The study evaluated 61 patients across two cohorts: 35 PRRT-naïve patients and 26 PRRT-exposed patients who had progressive disease after receiving up to four doses of 177Lu-DOTATATE. Benefits in key secondary endpoints, including progression-free survival and overall survival, were observed across both cohorts, with AlphaMedix demonstrating a manageable safety profile similar between groups.
Breakthrough Therapy Recognition and Clinical Significance
In February 2024, AlphaMedix was granted Breakthrough Therapy Designation by the US Food and Drug Administration for treatment of PRRT-naïve patients with unresectable or metastatic, progressive somatostatin receptor-expressing GEP-NETs, recognizing the potential clinical benefits of this lead-212-based therapy.
"The positive results from the ALPHAMEDIX-02 study represent a pivotal movement for the Orano Med 212Pb-based platform and underscore the profound potential of lead-212-based radiopharmaceuticals in addressing critical unmet needs for patients with GEP-NETs," said Volker Wagner, MD, PhD, Chief Medical Officer at Orano Med. "We are very encouraged by AlphaMedix's consistent and clinically meaningful activity across both peptide receptor radionuclide therapy (PRRT)-naïve and PRRT-exposed patients."
Study Design and Treatment Protocol
ALPHAMEDIX-02 is a phase 2, open-label, multicenter study evaluating the efficacy and safety of AlphaMedix in patients with histologically confirmed unresectable or metastatic GEP-NETs, positive somatostatin analogue imaging and at least one site of measurable disease. PRRT-exposed patients had received their last dose at least six months prior to Day 1.
In both cohorts, AlphaMedix was administered at 67.6 μCi/kg every eight weeks for up to four cycles, with a maximum of 6 mCi per cycle. Primary endpoints included overall response rate per RECIST1.1 and safety, while secondary endpoints included progression-free survival and overall survival.
Targeted Alpha Therapy Mechanism
Alpha-emitters are being studied to determine their relative potency and targeted tumor activity compared to current approved therapies. It is believed they could potentially reduce exposure of surrounding healthy tissue due to the short range of alpha particles. Orano Med develops targeted therapies against cancer using the unique properties of lead-212, an alpha-emitting radioisotope described as one of the more potent therapeutic payloads against cancer cells.
Disease Burden and Treatment Landscape
NETs are a heterogeneous group of cancers that originate from neuroendocrine cells, occurring mostly in the gastrointestinal tract and pancreas but also in other tissues including the thymus, lung, and other uncommon sites such as the ovaries, heart, and prostate. Most NETs strongly express somatostatin receptors.
Despite the global prevalence of NETs increasing each year, it is considered a rare cancer estimated to affect approximately 35/100,000 individuals worldwide. In the United States, around 12,000 patients annually are expected to be diagnosed with neuroendocrine tumors, with an average five-year survival rate of 60% at a metastatic stage.
Next Steps and Regulatory Path
"The promising ALPHAMEDIX-02 results represent a significant step forward, reinforcing the potential of targeted alpha therapy to deliver precise treatment for GEP-NETs," said Christopher Corsico, MD, Global Head of Development at Sanofi. "These data, demonstrating clinically meaningful activity and a manageable safety profile, underscore our unrelenting commitment to developing innovative therapies for patients with difficult-to-treat cancers."
The study is ongoing, and the full results will be presented at the 2025 European Society for Medical Oncology Congress. The results will also form the basis of discussions with health authorities. AlphaMedix has not been approved by any regulatory authority.
