PSMA is an ideal target for the precise diagnosis and treatment of prostate cancer. LNC1011 is a novel albumin-binding PSMA-targeted compound. This study aims to investigate the safety and efficacy of different doses of 225Ac-labeled LNC1011 in the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) and to explore the optimal therapeutic dose.
Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy has demonstrated considerable potential in the treatment of metastatic castration-resistant prostate cancer (mCRPC). By incorporating albumin-binding motifs into PSMA radioligands, the circulation time in the bloodstream can be prolonged, leading to significantly enhanced tumor uptake and therapeutic efficacy. LNC1011 employs dansylated Amino Acid as a novel, relatively weak yet high-performance albumin-binding moiety, achieving an optimal balance among increased tumor accumulation, improved safety, and refined diagnostic performance. This enables a unified theranostic approach within a single molecular framework. Alpha-emitting radionuclides, represented by Ac-225, generate alpha particles during decay. Their linear energy transfer is nearly 100-fold higher than that of β-emitters such as Lu-177, resulting in significantly enhanced tumor cell kill. This has earned them the designation of "scalpel-like radiotherapy." Moreover, alpha particles have an extremely short range (only a few cell diameters), causing minimal damage to surrounding normal tissues and almost no notable side effects, thereby conferring an excellent safety profile. In this clinical study, we will follow a "3+3" trial design to evaluate the safety and efficacy of different doses of 225Ac-LNC1011 in patients with mCRPC. The initial dose of 225Ac-LNC1011 is set at 3.70 MBq (100 μCi). Approximately three subjects will be enrolled at the current dose level. If no dose-limiting toxicity (DLT) is observed, the next cohort will receive an escalated dose of 5.55 MBq (150 μCi). If again no DLT occurs, the subsequent cohort will be escalated to 7.40 MBq (200 μCi), which is the planned maximum dose. It should be noted that if one DLT occurs at any dose level, three additional patients will be enrolled at the same dose. If only one DLT is observed among the total of six subjects, dose escalation may proceed. If two or more DLTs occur, dose de-escalation or trial termination will be initiated. Subjects in all dose cohorts will receive up to four treatment cycles at 8- to 12-week intervals. All participants will undergo safety follow-up during the trial and for 12 months after its completion.
Study Type
INTERVENTIONAL
administered intravenously once every 8-12 weeks (1 cycle) for up to 4 cycles
Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, China
RECRUITINGNumber 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)
Prostate-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)
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)
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Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
9