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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: 161Tb-LNC1011

Detailed 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).

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Zhaohui Zhu, MD; Phone Number: 86-13611093752; Email: 13611093752@163.com
• Study Contact Backup: Name: Zhengguo Chen, MD; Phone Number: 86-13908119175

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Peking Union Medical College Hospital
      • Contact: Zhaohui Zhu, MD; Phone Number: 86-13611093752; Email: 13611093752@163.com
  • Sichuan
    • Mianyang, Sichuan, China
      • Mianyang Central Hospital
      • Contact: Zhengguo Chen; Phone Number: 86-13908119175

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-Limiting Toxicities (DLTs)	Proportion of participants with DLTs per CTCAE v5.0 during the DLT window.	First 6 weeks after each initial dose at a given dose level
Maximum Tolerated Dose (MTD)	Highest dose level at which ≤1/6 participants experience a DLT.	At completion of dose escalation (approximately 12-18 months after study start)
Treatment-Emergent Adverse Events (TEAEs)	Number and grade of AEs/SAEs per CTCAE v5.0.	From first dose through 28 days after last dose (extended if related)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organ and Tumor Absorbed Doses (Dosimetry)	Absorbed doses to kidneys, salivary glands, tumor lesions, etc., derived from serial SPECT/CT.	Within first cycle (Day 0 to Day 7 imaging)
PSA50 and PSA90 Response Rates	Proportion achieving ≥50% and ≥90% PSA decline from baseline, confirmed per PCWG3.	Every 6 weeks during treatment and at end of treatment (up to approximately 24 weeks)

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Mianyang Central Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 23, 2025
• First Submitted That Met QC Criteria: January 27, 2026
• First Posted (Actual): February 2, 2026

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 27, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: PSMA; Radionuclide therapy; Metastatic castration-resistant prostate cancer; Terbium-161
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: PUMCH-MCH-161Tb-LNC1011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No