A novel targeted alpha therapy, ²²⁵Ac-LNC1011, has shown encouraging results in a phase 1 clinical trial for patients with PSMA-positive prostate cancer, according to data presented at the 2025 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting.

The trial, registered in China as ChiCTR2500095162, involved a small cohort of four patients and reported an objective response rate (ORR) of 50% under RECIST v1.1 criteria, with two patients showing partial responses and two maintaining stable disease. When assessed using PET-based PERCIST v1.0 criteria, the ORR increased to 75%. In all four patients, prostate-specific antigen (PSA) levels dropped significantly after treatment. One patient’s PSA fell from 7.885 ng/mL to 0.185 ng/mL, while another saw a reduction from 13.062 ng/mL to 1.057 ng/mL. At the time of reporting, median progression-free survival had not been reached, with follow-up ranging from 6 to 12 months. Additionally, three patients experienced improvements in their ECOG performance status, an important indicator of overall health and daily functioning.

The study also monitored safety and toxicity using CTCAE v5.0 guidelines and aimed to establish the maximum tolerable dose. Reported side effects were generally mild and manageable.

The trial enrolled adults with PSMA-positive prostate cancer confirmed through 68Ga-PSMA PET/CT imaging. Eligible participants also had to meet criteria for organ function and have an ECOG score of 2 or less. The initial dose level was set at 100 µCi.

With these early results, ²²⁵Ac-LNC1011 emerges as a potentially important addition to the arsenal against PSMA-positive prostate cancer.

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