UPDATE: ²²⁵Ac-LNC1011 Achieves 86.7% PSA50 Response in Early mCRPC Study

New results presented at EANM 2026 provide further evidence of the preliminary clinical activity of ²²⁵Ac-LNC1011, an experimental PSMA-targeted alpha radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC). We have previously discussed this therapy in this post.

Following the initial results, the new prospective study includes 15 patients previously treated with androgen receptor pathway inhibitors (ARPIs) and taxane chemotherapy. Patients received ²²⁵Ac-LNC1011 at a fixed dose of 3.7 MBq per cycle, administered every 8–10 weeks for up to four cycles.

The results showed a PSA reduction of at least 50% in 86.7% of patients (13/15), while 60% (9/15) achieved a PSA reduction of at least 90%. At the data cutoff, six patients had completed all four planned cycles, six had received three cycles, and three had received only one cycle.

The safety findings were also encouraging, with only one grade 3 adverse event reported: thrombocytopenia in one patient (6.7%), which led to a temporary treatment interruption. However, dry mouth (xerostomia) occurred in 80% of patients (12/15), although all cases were mild or moderate. Mild gastrointestinal symptoms were reported in 40% (6/15).

LNC1011 incorporates a chemical modification designed to prolong its circulation and potentially improve tumour exposure to the alpha-emitting radionuclide actinium-225.

Although these results suggest substantial preliminary PSA activity, the study remains small and non-randomised, with limited follow-up. PSA progression-free survival and overall survival data are not yet mature, and the findings cannot establish a survival benefit or superiority over other PSMA-targeted radioligand therapies.

These updated findings support further clinical investigation of ²²⁵Ac-LNC1011, particularly to determine whether its early PSA responses translate into durable disease control.

Source.