Phase 3 Trial for 177Lu-ludotadipep Radioligand Therapy for mCRPC

A new phase 3 trial is testing 177Lu-ludotadipep (177Lu-FC705 or, simply, FC705), an experimental PSMA-targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC). Unlike 177Lu-PSMA-617 (Pluvicto), ludotadipep includes an albumin-binding component designed to keep the radioligand in circulation longer and increase radiation delivery to PSMA-positive tumours.

Earlier studies suggest that this strategy may allow substantial tumour irradiation with relatively low administered activity. The dose selected for development was approximately half the activity administered per cycle with Pluvicto.

In the small phase 2 study, repeated treatment produced encouraging biochemical activity. Among 15 efficacy-evaluable patients, 46.7% achieved a confirmed PSA decline of at least 50%, while 73.3% achieved a PSA50 response at some point during treatment. Multi-cycle dosimetry also suggested that up to six administrations could remain within conventional radiation limits for major organs.

Imaging results require more caution. An initially reported 60% response rate was based on PSMA PET/CT assessment, whereas a later analysis using PCWG3-modified RECIST 1.1 produced an objective response rate of only 14.3%. However, 8 of 14 patients were not evaluable by RECIST, largely because they had bone-dominant disease without measurable soft-tissue lesions. The two RECIST responders were complete responses.

The new randomized study plans to enrol 114 men with progressive PSMA-positive mCRPC and compares ludotadipep plus best supportive or standard care with best supportive or standard care alone. Treatment is given every eight weeks for four cycles, with up to six cycles permitted in selected patients.

Clinical trial.