Efficacy and safety of Lu-177-DGUL in a phase 2 study of patients with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

209 Background: Prostate-specific membrane antigen (PSMA) is an integral membrane protein highly specific to the prostate. The prevalence of PSMA expression is more than 90% in prostate cancers. Lutetium (177Lu) DGUL is a radiopharmaceutical developed for the treatment of prostate cancer patients. DGUL is a small molecule with high binding affinity to PSMA, and while it selectively binds to prostate cancer cells upon labeling with Lu-177 and emits β-rays to cause damage, it minimizes damage to normal cells. Methods: This was an open-label, single-arm, multi-center, phase 1/2 study (NCT05547061). Key eligibility criteria included patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed after treatment with an androgen receptor pathway inhibitor (ARPI) with or without docetaxel, had at least one PSMA-positive lesion on baseline imaging using Ga-68-NGUL, and an ECOG performance status of ≤ 2. Patients received Lu-177-DGUL intravenously every 6 weeks for a maximum of 6 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Key secondary endpoints were disease control rate (DCR), prostate-specific antigen (PSA) response, and the incidence of adverse events. Results: In the phase 2 study, 121 patients were screened, of whom 91 were enrolled and treated with Lu-177-DGUL. The confirmed objective response rate (ORR) was 35.9% (7 complete responses, 21 partial responses), and the disease control rate (DCR) was 60.3%. The proportions of patients with a confirmed decrease in the PSA level of at least 50% and 80% from baseline were 66.7% (52/78) and 39.7% (31/78), respectively. In a subgroup analysis, the ORR was 41.9% (13/31) in pre-taxane patients and 31.9% (15/47) in post-taxane patients. Regarding safety, the most common treatment-emergent adverse events (occurring in ≥10% of patients) were anaemia (31.9%), dry mouth (13.2%), decreased appetite (12.1%), and nausea (11.0%). Conclusions: Lu-177-DGUL demonstrated promising anti-tumor activity and a manageable safety profile in PSMA-positive mCRPC. The consistent anti-tumor activity observed across subgroups, including pre- and post-taxane, highlights its potential as a robust treatment for mCRPC. Clinical trial information: NCT05547061 .