Efficacy and Safety of Disitamab Vedotin Plus Abiraterone for Metastatic Castration-Resistant Prostate Cancer：a Phase II Study

Nanjing University

Status and phase

Enrolling

Phase 2

Conditions

mCRPC

Treatments

Drug: Disitamab Vedotin (RC48)

Drug: Abiraterone + prednisone

Study type

Interventional

Funder types

Other

Identifiers

NCT07093866

IUNU-PC-125

Details and patient eligibility

About

This is an open-label，prospective，single-arm，phase 2 trial aims to evaluate the efficacy and safety of disitamab vedotin combined with abiraterone in patients with metastatic castration-resistant prostate cancer.

Enrollment

20 estimated patients

Sex

Male

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.