Prospective Clinical Trial of 177Lu-P17-088 in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) has demonstrated promising potential for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Conjugation of albumin-binding moieties to PSMA-targeted radioligands can prolong their circulating half-life in the blood, thereby markedly enhancing tumor uptake and therapeutic efficacy. P17-088 incorporates a pegylated p-iodophenylbutanoyl group as an albumin binder with moderate binding affinity yet superior overall performance, which achieves a refined balance between augmented tumor accumulation and favorable safety profiles. In our preliminary first-in-human study, 177Lu-P17-088 was observed to exhibit elevated distribution in organs including the red bone marrow and kidneys, with a considerably higher accumulation magnitude in tumor lesions. Satisfactory therapeutic outcomes were achieved even at a low activity dose of 1.11 GBq, validating its potential for further clinical translational research. This single-arm study is designed to further evaluate the safety and efficacy of low-dose 177Lu-P17-088 in mCRPC patients. 177Lu-P17-088 will be administered at a fixed activity of 3.7 GBq (±10%) once every 6 to 8 weeks, with a total of four planned treatment cycles. Post-treatment follow-up (safety and efficacy): Upon discontinuation of treatment, all enrolled participants will undergo systematic safety surveillance, including a 30-day short-term safety follow-up (FUP) assessment and extended long-term safety monitoring for approximately 12 months. Survival follow-up: Following the termination of study treatment or completion of the post-treatment follow-up period, participants' vital status will be collected via telephone contact every 90 days as part of survival surveillance. Strict adherence to the survival follow-up schedule shall be ensured to facilitate complete survival data acquisition. Survival follow-up and the overall study will be concluded once the required number of overall survival (OS) events for the final survival analysis is reached.