A Prospective, Open-label, Dose-Escalation, Single-Center Study to Evaluate the Safety, Biodistribution/Dosimetry and Preliminary Efficacy of 161Tb-LNC1011 in Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Incidence of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is a prospective, open-label, single-center, dose-escalation study using a standard 3+3 design to assess the safety, tolerability, biodistribution/dosimetry and preliminary efficacy of the albumin-binding PSMA radioligand 161Tb-LNC1011 in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients will receive intravenous 161Tb-LNC1011 starting at 50 mCi with planned dose-level escalations to 80, 130 and 200 mCi (±10%). Early dose levels (50 mCi) receive 1 cycle; later levels receive up to 4 cycles every 6 weeks based on safety and disease status. Primary endpoints include dose-limiting toxicities (DLTs), adverse events (AEs) graded by CTCAE v5.0, and determination of maximum tolerated dose (MTD). Secondary endpoints include organ/tumor absorbed doses, PSA responses (PSA50/PSA90), disease control, time to PSA progression and radiographic progression-free survival per PCWG3.
详细描述
Rationale: 161Tb emits β-particles plus abundant low-energy conversion/Auger electrons (very short range, high LET), potentially improving tumoricidal effect-especially for micrometastases-vs 177Lu. LNC1011 is a PSMA ligand with albumin-binding moiety designed to prolong circulation and enhance tumor uptake/retention. Preclinical and early clinical data support feasibility and safety.
Design: 3+3 dose-escalation. Dose levels (activity to be administered IV): 50 mCi (45-55), 80 mCi (72-88), 130 mCi (117-143), 200 mCi (180-220). DLT window: 6 weeks post-dose. If ≥2/6 DLTs, de-escalate; the prior dose is MTD.
Dosing/Cycles: Early dose level (50 mCi) one cycle; later levels up to 4 cycles q6 weeks. Retreatment contingent on hematologic recovery to CTCAE Grade ≤1 or baseline.
Imaging & Dosimetry: Post-dose SPECT/CT at ~30 min, 2 h, 8 h, 24 h, Day 2, Day 7 for time-activity curves and dosimetry. Disease assessments with 68Ga-PSMA-11 PET/CT and labs (PSA, hematology, chemistry) per schedule.
Safety Monitoring: Continuous AE/SAE recording from consent through 28 days post-last dose (or longer if related), DMC oversight (see below).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male, ≥18 years.
- •Pathologically confirmed mCRPC per PCWG
- •68Ga-PSMA-11 PET/CT positive.
- •Prior exposure to at least one novel androgen-axis drug (e.g., enzalutamide and/or abiraterone) or at least one taxane regimen, or intolerance/refusal to taxane chemotherapy.
- •ECOG 0-2; life expectancy ≥6 months.
- •Adequate organ function: ALT/AST ≤3× ULN; BUN/Cr ≤1.5× ULN; WBC ≥3.5×10^9/L; PLT ≥100×10^9/L; Hb ≥90 g/L.
- •Signed informed consent and willingness to comply with study procedures.
排除标准
- •Major trauma/surgery within 4 weeks prior to study treatment.
- •Active severe systemic or localized infection or other serious comorbidity.
- •Immunodeficiency or recent use of immunosuppressants/immunoenhancers, recent vaccines.
- •Autoimmune diseases (e.g., rheumatoid arthritis) requiring active management.
- •Uncontrolled arrhythmias (incl. Afib), heart failure NYHA > II, uncontrolled hypertension.
- •Known allergy to components of investigational product.
- •Positive syphilis, HBV/HCV/HIV.
- •Inadequate contraception in patients of reproductive potential.
- •Psychiatric illness compromising compliance.
- •Unable to undergo SPECT/CT or to retain urine for 30 minutes.
- •Any condition deemed unsuitable by the investigator.
研究组 & 干预措施
Dose-Escalation Cohort (3+3): 161Tb-LNC1011
Single-group, open-label, sequential dose escalation of 161Tb-LNC1011 (IV). Planned dose levels: 50, 80, 130, 200 mCi (±10%). At 50 mCi: 1 cycle; higher levels: up to 4 cycles every 6 weeks, contingent on safety and disease status. DLT window: 6 weeks post-dose; MTD per standard 3+3 rules (≥2/6 DLTs defines exceeding dose). Retreatment requires hematologic recovery to CTCAE ≤ Grade 1 or baseline. Post-dose SPECT/CT at ~30 min, 2 h, 8 h, 24 h, Day 2, Day 7 for dosimetry; disease assessments with 68Ga-PSMA-11 PET/CT and labs per schedule.
干预措施: 161Tb-LNC1011 (Drug)
结局指标
主要结局
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: First 6 weeks after each initial dose at a given dose level
Proportion of participants with DLTs per CTCAE v5.0 during the DLT window.
Maximum Tolerated Dose (MTD)
时间窗: At completion of dose escalation (approximately 12-18 months after study start)
Highest dose level at which ≤1/6 participants experience a DLT.
Treatment-Emergent Adverse Events (TEAEs)
时间窗: From first dose through 28 days after last dose (extended if related)
Number and grade of AEs/SAEs per CTCAE v5.0.
次要结局
- Organ and Tumor Absorbed Doses (Dosimetry)(Within first cycle (Day 0 to Day 7 imaging))
- PSA50 and PSA90 Response Rates(Every 6 weeks during treatment and at end of treatment (up to approximately 24 weeks))