Prospective Clinical Trial of 225Ac-LNC1011 in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria18

• Metastatic Castration-Resistant Prostate Cancer (mCRPC) mCRPC refers to prostate cancer that progresses despite serum testosterone at castrate levels (\< 50 ng/dL or 1.7 nmol/L), meeting at least one of the following criteria:
• PSA \>1 ng/mL with two consecutive rises at least 1 week apart, each increase ≥50% above the nadir.
• Radiographic progression: Either two or more new bone lesions on bone scan, or soft tissue lesion progression as per RECIST 1.1 criteria. Progression based on symptoms alone is insufficient for mCRPC diagnosis and requires further evaluation.
• Failure of, Refusal of, Absence of, or Refractoriness to Standard Therapy, or Disease Progression, or No Available Standard Therapy per Current Guidelines:
• Patients who have not received, refused, or progressed after receiving at least 1 but no more than 2 prior taxane-based therapies. The taxane regimen must have included exposure for at least 2 cycles. Patients who received only one taxane may be included if the investigator deems them unsuitable for a second taxane (e.g., due to frailty assessed by geriatric/comorbidity evaluation or intolerance).
• Patients who have progressed after receiving at least one novel androgen axis drug \[NAAD\] (e.g., abiraterone, enzalutamide).
• Ability to understand and voluntarily sign a written informed consent form (ICF), and willingness and ability to comply with trial procedures including examinations and follow-up.
• Age 18-90 years (inclusive).
• Expected survival \> 6 months.
• ECOG performance status ≤ 2.
• Presence of high-uptake lesions confirmed by 68Ga-PSMA-11 PET/CT imaging (positive defined as lesion uptake \>1.5 times the liver background).
• At least one measurable lesion per RECIST 1.1 criteria OR at least one bone metastasis per PCWG3 criteria.
• Adequate organ function (No blood products, growth factors, or albumin administered within 14 days prior to baseline lab tests):
• Bone Marrow Function: Neutrophil count ≥ 1.5 × 10⁹/L, White blood cell count ≥ 3.0 × 10⁹/L, Platelet count ≥ 100 × 10⁹/L, Hemoglobin ≥ 10 g/dL (≥ 100 g/L).
• Liver Function: Albumin ≥ 30 g/L, Total bilirubin ≤ 1.5 × ULN, ALT or AST ≤ 3.0 × ULN (without liver metastases) or ≤ 5.0 × ULN (with liver metastases).
• Renal Function: Serum creatinine ≤ 1.5 × ULN.
• Coagulation: INR ≤ 1.5; Activated partial thromboplastin time (APTT) ≤ 2 × ULN (for patients not on anticoagulation or on stable-dose anticoagulation).
• Agreement to comply with prescribed radiation protection measures during the trial period.