ALPHAMEDIX-02: Unexpected Efficacy and Safety Considerations in PRRT-Naive Patients

Following the 2025 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium, Mary Maluccio, MD, MPH, FACS, Louisiana State University School of Medicine, recaps and reflects on her presentation of follow-up efficacy and safety data of peptide receptor radionuclide therapy (PRRT)-naive patients with SSTR-expressing, unresectable or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) from the phase 2 ALPHAMEDIX-02 trial (NCT05153772), in an interview with Targeted Oncology.

Read the full interview here.

The ALPHAMEDIX-02 trial is evaluating the efficacy and safety of ²¹²Pb-DOTAMTATE (AlphaMedix), an investigational targeted alpha particle radioligand therapy. Regarding efficacy, compared with other radioligand therapy options which typically show objective response rates (ORRs) around 15% to 20%, the agent demonstrated remarkable efficacy in this most recent readout, with ORRs rising to well above 50% in both PRRT-naive patients and those who had previously received beta particle radioligand therapy.

Specifically, in the PRRT-naive cohort, the ORR reached 60%, while 34.1% of patients showed stable disease. Combining these results, the overall disease control rate achieved was around 94.3%, a result deemed “unexpectedly good” by Dr Maluccio.

Dr Maluccio also highlights 2 safety issues to be evaluated more closely in the imminent phase 3 trial: renal toxicity and dysphagia. Renal toxicity, which is inherent to radioligand therapy, was not reported as a significant issue with beta particles. On the other hand, alpha particles are likely associated with more renal toxicity, potentially manifesting in patients with elevated creatinine levels or in those who developed chronic kidney disease over the course of treatment. Although centers like the New Orleans program did not see patients requiring significant medical intervention, the protocol may need to change how patients are treated during initial recovery following each dose to reduce toxicity across sites.

The second key safety discussion centered on dysphagia, which Maluccio describes as “somewhat unexpected, and … a little bit difficult for us to understand what that means in the context of a treatment that … wouldn’t have necessarily led to a functional, esophageal or gastroesophageal dysfunction.” With this new consideration, the phase 3 trial plans to incorporate greater sensitivity to patients’ comorbid conditions that may predispose them to dysphagia. Specific strategies outlined by Dr Maluccio include standardizing evaluations of patients during or after treatment or Botox injections.