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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
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.
Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
Mianyang Central Hospital
Mianyang, Sichuan, China
Incidence of Dose-Limiting Toxicities (DLTs)
Proportion of participants with DLTs per CTCAE v5.0 during the DLT window.
Time frame: 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.
Time frame: 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.
Time frame: From first dose through 28 days after last dose (extended if related)
Organ and Tumor Absorbed Doses (Dosimetry)
Absorbed doses to kidneys, salivary glands, tumor lesions, etc., derived from serial SPECT/CT.
Time frame: 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.
Time frame: Every 6 weeks during treatment and at end of treatment (up to approximately 24 weeks)
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