Prostate Cancer
Conditions
Keywords
Terbium-161, PSMA, Radionuclide therapy, Metastatic castration-resistant prostate cancer
Brief summary
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.
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).
Interventions
DRUG161Tb-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.
Sponsors
Peking Union Medical College Hospital
Mianyang Central Hospital
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) | 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) | 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) | From first dose through 28 days after last dose (extended if related) | Number and grade of AEs/SAEs per CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Organ and Tumor Absorbed Doses (Dosimetry) | Within first cycle (Day 0 to Day 7 imaging) | Absorbed doses to kidneys, salivary glands, tumor lesions, etc., derived from serial SPECT/CT. |
| PSA50 and PSA90 Response Rates | Every 6 weeks during treatment and at end of treatment (up to approximately 24 weeks) | Proportion achieving ≥50% and ≥90% PSA decline from baseline, confirmed per PCWG3. |
Countries
China
Contacts
CONTACTZhaohui Zhu, MD
CONTACTZhengguo Chen, MD
Outcome results
None listed