NCT07117760

Prospective Clinical Trial of 225Ac-LNC1011 in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Prospective Clinical Trial of Low-dose 225Ac-LNC1011 in the Treatment of Metastatic Castration-Resistant Prostate Cancer

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: First Affiliated Hospital of Fujian Medical University · Academic / Other
• Sex: Male
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

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.

Conditions

• Prostate Cancer

Interventions

Type	Name	Description
DRUG	225Ac-LNC1011	administered intravenously once every 8-10 weeks (1 cycle) for 4 cycles
DRUG	68Ga-PSMA-11	Intravenous dose of approx. 150 MBq at screening and at time of centrally confirmed radiographic progressive disease

Timeline

• Start date: 2025-04-22
• Primary completion: 2027-12-31
• Completion: 2029-12-31
• First posted: 2025-08-12
• Last updated: 2025-08-12

Locations

1 site across 1 country: China