Safety, Tolerability and Preliminary Efficacy of 161Tb-LNC1011 (PSMA Radioligand) in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Официальное название

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

Обзор

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.

Подробное описание

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).

Вмешательства

• Препарат 161Tb-LNC1011
  Intravenous administration; planned dose levels: 50, 80, 130, 200 mCi (±10%); cycle interval q6 weeks; up to 1 cycle at 50 mCi and up to 4 cycles at later dose levels as permitted by safety and disease status.

Первичные конечные точки

• Incidence of Dose-Limiting Toxicities (DLTs) [Срок оценки: First 6 weeks after each initial dose at a given dose level]
• Maximum Tolerated Dose (MTD) [Срок оценки: At completion of dose escalation (approximately 12-18 months after study start)]
• Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: From first dose through 28 days after last dose (extended if related)]

Вторичные конечные точки (2)

• Organ and Tumor Absorbed Doses (Dosimetry) [Срок оценки: Within first cycle (Day 0 to Day 7 imaging)]
• PSA50 and PSA90 Response Rates [Срок оценки: Every 6 weeks during treatment and at end of treatment (up to approximately 24 weeks)]

Критерии участия

Критерии включения

• Male, ≥18 years.
• Pathologically confirmed mCRPC per PCWG3.
• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Peking Union Medical College Hospital — Пекин
• Mianyang Central Hospital — Mianyang

Идентификаторы

NCT: NCT07381582 · PUMCH-MCH-161Tb-LNC1011

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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