212Pb-Dotamtate Prolongs Responses in Advanced GEP-NETs

Lead Pb 212 (²¹²Pb)-dotamtate (AlphaMedix), an investigational somatostatin receptor (SSTR)–targeted α therapy, produced meaningful overall response rates (ORRs) and prolonged clinical benefit among patients with unresectable or metastatic SSTR-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) regardless of previous peptide receptor radionuclide therapy (PRRT) receipt in the phase 2 ALPHAMEDIX02 study (NCT05153772), according to a news release from the developers, Sanofi Winthrop Industrie.¹

Furthermore, investigators found benefits in key secondary survival end points, including progression-free survival (PFS) and overall survival (OS), across PRRT-naive and PRRT-exposed populations. Additionally, ²¹²Pb-dotamtate demonstrated a manageable safety profile across both patient groups.

"The positive results from the ALPHAMEDIX02 study represent a pivotal movement for the Orano Med ²¹²Pb-based platform and underscore the profound potential of ²¹²Pb-based radiopharmaceuticals in addressing critical unmet needs for patients with GEP-NETs. We are [quite] encouraged by AlphaMedix's consistent and clinically meaningful activity across both PRRT-naive and PRRT-exposed [populations],” Volker Wagner, MD, PhD, chief medical officer at Orano Med, said in the news release.¹ “These data reinforce our belief that delivering highly potent α-emitters directly to cancer cells could potentially offer a meaningful new treatment option for people living with GEP-NETs.”

The open-label phase 2 study evaluated ²¹²Pb-dotamtate in patients with histologically confirmed unresectable or metastatic GEP-NETs, at least 1 site of measurable disease, and positive somatostatin analogue imaging. The study included 2 cohorts stratified by prior receipt of PRRT, with those exposed to PRRT having received up to 4 doses of lutetium Lu 177-dotatate (Lutathera), receiving their last dose at least 6 months prior to the start of study treatment. ²¹²Pb-dotamtate was administered every 8 weeks for a maximum of 4 cycles at 67.6 μCi/kg, with a cycle not exceeding 6 mCi.

The primary end points of the study included ORR per RECIST v.1.1 criteria and safety. Secondary end points included PFS, OS, time to tumor progression, and health-related quality of life.²

The study is currently ongoing, and full results are expected to be presented at the 2025 European Society for Medical Oncology Congress, which will form the basis of discussions with regulatory authorities.

"The promising ALPHAMEDIX02 results represent a significant step forward, reinforcing the potential of targeted α therapy to deliver precise treatment for GEP-NETs,” said Christopher Corsico, MD, global head of development at Sanofi, in the release.¹ “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. We look forward to advancing AlphaMedix and working with Orano Med and regulators to bring this important treatment to the GEP-NET community as soon as possible.”

Patients 18 years or older with progression after somatostatin analogue therapy, confirmed presence of somatostatin receptors on all lesions, an ECOG performance status of 0 or 2, sufficient bone marrow capacity and organ function, and a life expectancy of at least 12 weeks at the time of screening were eligible for study enrollment.

Those ineligible for study enrollment included those who received prior whole-body irradiation or PRRT using select agents or targeted α therapy; those who received prior regional hepatic radionuclide therapy within 4 months of enrollment; those with a known hypersensitivity to somatostatin analogues, amino acid infusion, or ²¹²Pb-dotamtate; or those who received any somatostatin analogue within 1 day prior to cycle 1, day 1 of treatment. Additional exclusion criteria included a history of myelodysplastic syndrome, an indication for surgical lesion removal with curative intent, known brain metastases not treated and/or stable for at least 6 months, and other known coexisting malignancies except nonmelanoma skin cancer or carcinoma in situ of the uterine cervix.

References

1. AlphaMedix (212Pb-dotamtate) achieved all primary efficacy endpoints in phase 2 study, demonstrating clinically meaningful benefits in patients with gastroenteropancreatic neuroendocrine tumors. News release. Sanofi Winthrop Industie. October 8, 2025. Accessed October 9, 2025. https://tinyurl.com/2cwmm2m6
2. Targeted alpha-emitter therapy of PRRT naïve and previous PRRT neuroendocrine tumor patients (ALPHAMEDIX02). ClinicalTrials.gov. Updated June 4, 2025. Accessed October 9, 2025. https://tinyurl.com/ye2565b2