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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Prostate Cancer

Treatments: Drug: 161Tb-LNC1011

Study type: Interventional

Funder types: Other

Identifiers

NCT07381582

PUMCH-MCH-161Tb-LNC1011

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 15 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

---

15 participants in 1 patient group

Dose-Escalation Cohort (3+3): 161Tb-LNC1011

Experimental group

Description:

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.

Treatment:

Drug: 161Tb-LNC1011