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

Abstract

[177Lu]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 [177Lu]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. [177Lu]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 [18F]Florastamin was obtained at baseline and again at weeks 4 and 8. The subjects required positive PSMA PET/CT prior to [177Lu]Ludotadipep administration. Among the 29 subjects who received [177Lu]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 [177Lu]Ludotadipep. These data thus far suggest that [177Lu]Ludotadipep could be a promising RPT agent with low toxicity in mCRPC patients who have not been responsive to conventional treatments.

PSMA Radioligand Therapy in Prostate Cancer

“…The NCT04509557 trial tested 177 Lu-ludotadipep, a novel PSMA targeting therapeutic agent with albumin binding moiety that allows longer circulation time, in 29 mCRPC patients. The escalation protocol with a single dose ranging between 1.9 and 5.6 GBq in 24 patients with positive 18 F-florastamin PET/CT and full follow-up demonstrated that treatment was safe (10.3% AE) with any PSA decrease in 66.7% and PSA50 in 37.5% 57 …”

“…The escalation protocol with a single dose ranging between 1.9 and 5.6 GBq in 24 patients with positive 18 F-florastamin PET/CT and full follow-up demonstrated that treatment was safe (10.3% AE) with any PSA decrease in 66.7% and PSA50 in 37.5%. 57 The NCT03780075 trial presented results of 28 mCRPC patients divided into 3 groups (A, B, and C) treated with 177 Lu-EB-PSMA-617. This new molecule conjugates a truncated Evans blue to DOTA with the objective of increasing tumor accumulation and retention and reducing the dosage of 177 Lu.…”

“…In December 2022, Novartis announced a positive result in the primary end point (rPFS) in benefit of 177 Lu-PSMA-617 compared with a change in ARTA, but further details are expected later this year. 56 On-Going Trials With Other PSMA Molecules and/or Isotopes as Single Therapy for RLT for mCRPC Currently, there are available results of only two 57,58 of the 11 on-going clinical phase 1-2 trials that investigate new PSMA molecules and/or isotopes as single therapy, all in mCRPC scenario. [59][60][61][62][63][64][65][66][67] The evidence is summarized in Supplementary Table S2, http://links.…”

“…Currently, there are available results of only two 57,58 of the 11 on-going clinical phase 1–2 trials that investigate new PSMA molecules and/or isotopes as single therapy, all in mCRPC scenario 59–67 . The evidence is summarized in Supplementary Table S2, http://links.lww.com/CNM/A439.…”

Current clinical application of lutetium‑177 in solid tumors (Review)

“…Overall 16 (66.7%) of the 24 participants with complete 12-week follow-up data showed a reduction in PSA levels, and nine (37.5%) of those subjects showed a PSA decline of ≥50%. At the 12th week after receiving a single dosage of 177 Lu Ludotadipep, five of the 24 patients (20.8%) displayed disease progression (a ≥25% increase in PSA levels from the baseline), suggesting that 177 Lu Ludotadipep may be a promising new treatment for mCRPC ( 34 ).…”