Disitamab Vedotina más Abiraterona para el Tratamiento del Cáncer de Próstata Resistente a la Castración Metastásico

Fecha de inicio: 20 de julio de 2025

Inclusion Criteria: * Patients are able to understand and voluntarily sign the informed consent form (ICF); judged by the investigator to be capable of complying with the protocol. * Male patients of ≥18 years or older at the time of ICF signature. * Patients with ECOG performance status 0-1. * Patients with an expected survival of 3months or more. * Patients who are histologically or cytologically confirmed prostatic adenocarcinoma with HER2 expression (IHC 1+, 2+ or 3+) in archival or fresh tumour tissue. * Patients with documented castration-resistant prostate cancer (CRPC): serum testosterone \<1.73 nmol/L (50 ng/dL) at screening; patients on medical castration must continue LHRH agonist/antagonist therapy throughout the study. * Patients with evidence of metastatic disease by bone scan (bone lesions) and/or CT/MRI (soft-tissue lesions). * Patients with adequate organ function as defined below: * Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L * Platelet count (PLT) ≥100 × 10⁹/L * Hemoglobin (Hb) ≥100 g/L * Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); ≤2 × ULN if liver metastases present * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 × ULN; ≤2 × ULN if liver metastases present * Serum creatinine (Cr) ≤1.5 × ULN or calculated creatinine clearance (CrCl) ≥60 mL/min (Cockcroft-Gault formula; calculate only if Cr \>1.5 × ULN) * Urinalysis protein \<2+; if ≥2+, 24-h urine protein must be \<1 g or urine protein/creatinine ratio \<0.5 * For patients not on anticoagulation: INR and aPTT ≤1.5 × ULN; patients on stable-dose anticoagulation are eligible * Left ventricular ejection fraction (LVEF) ≥50% or ≥local lower limit of normal (LLN), whichever is lower * QTcF interval \<470 ms * Male patients with partners of child-bearing potential must use a medically acceptable contraceptive method from the first study dose until 3 months after the last dose. Exclusion Criteria: * Patients who are known hypersensitivity to any component of disitamab vedotin or abiraterone. * Patients with other malignancies within 3 years before screening, except early-stage malignancies considered clinically cured (carcinoma in situ or stage I tumors), e.g., basal-cell or squamous-cell skin carcinoma or superficial bladder cancer. * Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with treated brain metastases may enroll if lesions have been stable for ≥1 month, there is no evidence of new or enlarging CNS disease, and systemic corticosteroids have been discontinued ≥3 days before the first study dose. * Patients who are clinically significant pericardial effusion, or pleural/peritoneal/pelvic effusions that are poorly controlled or require drainage within 2 weeks before the first dose. * Patients with major surgical intervention (any grade 3 or 4 procedure per the 2009 Chinese Regulation on Clinical Application of Medical Technologies) within 4 weeks before the first dose, or incomplete post-operative recovery that, in the investigator's judgment, poses a risk to trial participation. * Patients who are prior PSMA-targeted therapy. * Patients within 4 weeks (6 weeks for nitrosoureas or mitomycin C) before the first dose: any antineoplastic chemotherapy (except castration therapy), radiotherapy (\>1 week of local palliative radiotherapy permitted), endocrine therapy (estrogens or anti-androgens; bicalutamide or nilutamide require 6-week washout), targeted therapy, immunotherapy, or participation in another interventional clinical trial (observational studies or post-trial follow-up are allowed). * Patients with stable-dose denosumab or bisphosphonates for bone metastases are permitted. * mCRPC patients must not have used PSA-lowering herbal agents (e.g., saw palmetto) or systemic corticosteroids (except short courses for allergy prophylaxis/treatment) within 4 weeks before the first dose, nor plan to use such agents during the study. * Patients with use of antineoplastic traditional Chinese medicine (TCM) prescriptions or proprietary TCM within 1 week, or receipt of blood transfusion/blood products, hematopoietic growth factors, or other agents to correct blood cell counts within 2 weeks before first study dose. * Patients with toxicities from prior antineoplastic therapy that have not resolved to baseline, CTCAE v5.0 grade 0-1 (except alopecia and pigmentation), or to the levels specified in the inclusion/exclusion criteria; unhealed wounds. Irreversible toxicities not expected to worsen with study drug (e.g., hearing loss) are permitted. * Patients with unexplained fever \>38.5 °C (tumor-related fever may be allowed per investigator judgment); active or persistent infection; HIV antibody positive; HBsAg positive with HBV DNA \> site ULN, or HBsAg-negative/HBcAb-positive with HBV DNA \> site ULN after treatment; HCV antibody positive with HCV RNA \> site ULN; active syphilis (except adequately treated, cured, or stable syphilis). * NYHA class III/IV congestive heart failure; uncontrolled arrhythmia despite treatment/intervention; risk of QT prolongation or use of drugs known to prolong QT; refractory hypertension (hypertension controlled to \<140/90 mmHg on medication is allowed). * Patients with clinically significant vascular events within 6 months before first dose, including acute arterial/venous thromboembolism, thrombotic arteritis, thrombophlebitis, acute pulmonary embolism, acute coronary syndrome (MI, unstable angina, etc.), acute cerebrovascular events, or disseminated intravascular coagulation. * Patients with tumor metastases with clear invasion of major arteries posing a high bleeding risk. * Patients with interstitial pneumonitis, pulmonary fibrosis, or other severe pulmonary disease requiring treatment; hemoptysis \>2.5 mL per episode within 3 weeks before first dose. * Patients with active gastro-intestinal ulcer, perforation, and/or fistula requiring treatment within 6 months; GI bleeding (hematemesis, melena, or hematochezia) within 3 months without endoscopic/colonoscopic evidence of complete healing. * Patients with uncontrolled concurrent disease \>CTCAE v5.0 grade 2 (e.g., diabetes). Uncontrolled concurrent disease \>CTCAE v5.0 grade 2 (e.g., diabetes). * Patients with CTCAE v5.0 grade \>2 peripheral neuropathy, prior epilepsy, psychiatric disorders; history of drug abuse within 6 months or alcohol abuse within 3 months (alcohol abuse defined as \>14 units/week: 1 unit = 285 mL beer, 25 mL spirits, or 80 mL wine). * Patients with autoimmune disease, immunodeficiency, or organ transplantation. * Patients with any condition, therapy, or laboratory abnormality that, in the investigator's opinion, could confound results, interfere with trial participation, or be not in the subject's best interest.