A Single Dose of Novel PSMA-Targeting Radiopharmaceutical Agent [(177)Lu]Ludotadipep for Patients with Metastatic Castration-Resistant Prostate Cancer: Phase I Clinical Trial

SIMPLE SUMMARY: Prostate specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed in prostate cancer cells. For patients with metastatic castration-resistant prostate cancer (mCRPC) who do not respond to conventional treatment, PSMA targeting radiopharmaceutical therapy (RPT) has recently been in the spotlight. [(177)Lu]Ludotadipep is a novel PSMA-targeting therapeutic agent designed with an albumin motif in order to increase the circulation time and uptake in the tumors. The safety and efficacy of [(177)Lu]Ludotadipep were evaluated through a phase I trial. ABSTRACT: [(177)Lu]Ludotadipep, which enables targeted delivery of beta-particle radiation to prostate tumor cells, had been suggested as a promising therapeutic option for mCRPC. From November 2020 to March 2022, a total of 30 patients were enrolled for single dose of [(177)Lu]Ludotadipep RPT, 6 subjects in each of the 5 different activity groups of 1.9 GBq, 2.8 GBq, 3.7 GBq, 4.6 GBq, and 5.6 GBq. [(177)Lu]Ludotadipep was administered via venous injection, and patients were hospitalized for three days to monitor for any adverse effects. Serum PSA levels were followed up at weeks 1, 2, 3, 4, 6, 8, and 12, and PSMA PET/CT with [(18)F]Florastamin was obtained at baseline and again at weeks 4 and 8. The subjects required positive PSMA PET/CT prior to [(177)Lu]Ludotadipep administration. Among the 29 subjects who received [(177)Lu]Ludotadipep, 36 treatment emergent adverse events (TEAEs) occurred in 17 subjects (58.6%) and 4 adverse drug reactions (ADRs) in 3 subjects (10.3%). Of the total 24 subjects who had full 12-week follow-up data, 16 (66.7%) showed decrease in PSA of any magnitude, and 9 (37.5%) showed a decrease in PSA by 50% or greater. A total of 5 of the 24 patients (20.8%) showed disease progression (PSA increase of 25% or higher from the baseline) at the 12th week following single dose of [(177)Lu]Ludotadipep. These data thus far suggest that [(177)Lu]Ludotadipep could be a promising RPT agent with low toxicity in mCRPC patients who have not been responsive to conventional treatments.