PSMA is an ideal target for precision diagnosis and treatment of prostate cancer. LNC1011 is a novel albumin-binding PSMA-targeted radioligand. This study aims to explore the safety and efficacy of 225Ac-labeled LNC1011 for treating patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC).
Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy has demonstrated promising potential in treating metastatic castration-resistant prostate cancer (mCRPC). Modification of PSMA radioligans with albumin-binding motifs prolonging blood circulation significantly enhances tumor uptake and therapeutic efficacy. LNC1011 incorporates dansylated amino acids as a novel, relatively weaker and superior albumin binder, achieving a refined balance between increased tumor accumulation, safety, and diagnostic performance. This enables a unified theranostic approach within a single molecular framework. Alpha-emitting radionuclide therapeutics offer unique advantages for cancer treatment. Regarding tumoricidal effects: Alpha emitters generate alpha particles during decay, possessing a linear energy transfer (LET) nearly 100 times higher than beta emitters, resulting in significantly superior tumor eradication. Beta emitters primarily cause single-strand DNA breaks, potentially allowing tumor cell repair and recurrence. In contrast, alpha emitters directly induce irreparable double-strand DNA breaks, leading to permanent tumor cell kill. This has earned them the designation "surgical knife-like radiotherapy." Furthermore, clinical trial data indicate that alpha emitters can trigger tumor immune responses while killing cancer cells, demonstrating synergistic effects with immunotherapy and achieving a "1 + 1 \> 2" outcome in cancer therapy. Regarding safety: Alpha particles have an extremely short range (a few cell diameters), causing minimal damage to surrounding normal tissues with almost negligible side effects, thus offering superior safety. Actinium-225 has a half-life of 9.92 days. During this period, it decays through a series of alpha and beta decays, maximizing its therapeutic potential. In this single-arm study, we will investigate the safety and efficacy of low-dose 225Ac-LNC1011 for the treatment of mCRPC. 225Ac-LNC1011 is administered at the dose of 3.7 MBq (+/- 10%), once every 8-10 weeks for a planned 4 cycles.. Post-Treatment Follow-up (Safety \& Efficacy): Following treatment cessation, all participants will undergo safety follow-up, including a 30-day safety follow-up visit (FUP) and longer-term safety follow-up assessments over approximately 12 months. Survival Follow-up: After discontinuation of study treatment or completion of the post-treatment follow-up period, participant status will be collected every 90 days (through telephone) as part of survival follow-up. Every effort should be made to adhere to the survival follow-up schedule to ensure collection of survival data. Survival follow-up and the study will conclude when the number of OS events required for the final OS analysis is reached.
administered intravenously once every 8-10 weeks (1 cycle) for 4 cycles
Intravenous dose of approx. 150 MBq at screening and at time of centrally confirmed radiographic progressive disease
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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Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20