PSMA is an ideal target for precision diagnosis and treatment of prostate cancer. P17-088 is a novel albumin-binding PSMA-targeted radioligand. This study aims to explore the safety and efficacy of 177Lu-labeled P17-088 for treating patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC).
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.
Study Type
INTERVENTIONAL
Allocation
NA
administered intravenously once every 6-8 weeks (1 cycle) for 4 cycles
Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, China
RECRUITINGProstate-specific antigen 50 (PSA50) response
PSA50 response is defined as the proportion of patients who have a more/equal 50% decrease in PSA from baseline, it will be calculated at 12, 24 and 48 months
Time frame: From date of randomization till 30 days safety fup, assessed up to 50 months (estimated final OS analysis)
Number of participants with Treatment Emergent Adverse Events
The distribution of adverse events (AE) will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Time frame: From enrollment till 30 days safety follow-up, assessed up to 50 months (estimated final OS analysis)
Progression Free Survival (PFS)
PSA-PFS is defined as the time from date of enrollment to the date of first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) or death from any cause, whichever occurs first.
Time frame: From date of enrollment until date of progression or date of death from any cause, whichever come first, assessed up to 50 months (estimated final OS analysis)
Overall Survival (OS)
OS is defined as time to death for any cause.
Time frame: From date of enrollment until date of death from any cause, assessed up to 50 months (estimated final OS analysis)
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Purpose
TREATMENT
Masking
NONE
Enrollment
20