Managing Safety in ALPHAMEDIX-02: Emerging Renal and Esophageal Toxicities

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, highlights key adverse events (AEs) observed throughout treatment of patients with ²¹²Pb-DOTAMTATE (AlphaMedix) in the phase 2 ALPHAMEDIX-02 trial (NCT05153772).

Watch the first part of Dr Strosberg’s interview.

The safety profile of ²¹²Pb-DOTAMTATE revealed expected, predominantly mild (grade 1 and grade 2) short-term AEs including alopecia, nausea, and fatigue. While cytopenias were generally not severe, there was a high frequency of lymphopenia, including some grade 3 and grade 4 cases. However, these cases were deemed as “not very clinically significant” by Dr Strosberg.

Perhaps more notably, the ALPHAMEDIX-02 trial brought to light various significant and unique long-term toxicities. The first key concern is renal insufficiency, a late toxicity that begins to develop after treatment completion. This complication was observed more frequently in the treatment-naive cohort compared with the treatment-refractory cohort, a difference likely attributable to the naive group having a longer follow-up period. Approximately 17% of patients in the naive cohort experienced grade 3 or grade 4 renal toxicity. The extent of renal sufficiency requires further investigation in extended follow-up, according to Dr Strosberg.

Secondly, achalasia was seen in some patients, manifesting as difficulty swallowing. Achalasia is a chronic condition, necessitating treatment with Botox injections for temporary relief and sometimes even surgical procedures. While the mechanism driving this AE remains unknown, Dr Strosberg suggests the potential role of somatostatin receptor expression in the myenteric plexus.

Overall, while the safety data indicate manageable short-term AEs, the potential for long-term renal toxicity and achalasia are critical considerations requiring ongoing follow-up and monitoring.

Read the full interview here.