A Multicenter Open Phase Ib to Evaluate the Safety, Efficacy and Pharmacokinetic Characteristics of Disitamab Vedotin in the Treatment With HER2- Expression, Gene Amplification or Mutation Metastatic Castration-Resistant Prostate Cancer

RC48-C034

The purpose of this study is to evaluate the safety and tolerance of Disitamab Vedotin in subjects with metastatic Castration-resistant prostate cancer.

2024-04-08

2025-12-01

2026-06-01

Recruiting

Early phase I

60

Inclusion Criteria: 1. Age ≥ 18 years 2. Histologically or cytologically confirmed adenocarcinoma of the prostate without histological features of small cells, neuroendocrine differentiation or signet-ring cell carcinoma cells 3. Presence of imaging-proven distant metastases from prostate cancer 4. mCRPC Subjects with prostate cancer progression during androgen deprivation therapy (or bilateral scrotal resection). Progression will be determined based on at least 1 of the following criteria (PCWG3 criteria): PSA progression: defined as 2 consecutive increases in PSA, separated by at least 1 week, relative to the previous reference value. If a confirmed PSA increase is the only indicator of progression, then 1 ng/mL is the minimum starting value; Soft tissue progression: defined as an increase of ≥20% in the sum of the diameters of all target lesions (short-axis for lymph node lesions and long-axis for non-lymph node lesions) relative to the sum of the smallest diameters at the start of treatment or the presence of one or more new lesions; Bone lesion progression: defined as the detection of at least two additional new lesions on bone scan. 5. Serum testosterone level ≤ 50 ng/dL (or ≤ 1.73 nmol/L), prior to the first study drug administration; 6. Continuous androgen deprivation therapy (ADT) with LHRH agonists or LHRH antagonists or previous bilateral orchiectomy (surgical debridement) during the study period; 7. Confirmed HER2 expression (IHC 1+, 2+, 3+), HER2 gene amplification, or HER2 gene mutation; 8. Subjects without the test results of HER2 expression, HER2 gene amplification or HER2 gene mutation will be required to provide sufficient tumour tissue samples for HER2 immunohistochemistry and NGS; 9. Previous treatment with at least one novel hormone therapy (e.g. abiraterone, enzalutamide) for metastatic hormone-sensitive prostate cancer (mHSPC) or mCRPC and have developed disease progression or intolerance to the drug, and: Cohort 1: no treatment regimen with a taxanes-containing agent in the mCRPC stage (no restriction in the metastatic or localised HSPC stage); and Cohort 2: a treatment regimen with at least one taxanes-containing agent, e.g. docetaxel, in the mCRPC stage; 10. Have at least one measurable target lesion according to RECIST v1.1 criteria; 11. The following criteria should be met within 7 days prior to the first study dose: 1. haemoglobin ≥ 9 g/dL; 2. absolute neutrophil count (ANC) ≥ 1.5 × 109/L; 3. platelet count ≥ 100 × 109/L; 4. serum total bilirubin ≤ 1.5 times the upper limit of normal (ULN); 5. without liver metastasis, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × ULN; with liver metastasis, alanine aminotransferase and aspartate aminotransferase ≤ 5 × ULN;; 6. albumin (ALB) ≥ 25 g/L; 7. blood creatinine ≤ 1.5 × ULN, or calculated according to the Cockcroft-Gault formula, creatinine clearance (CrCl) ≥ 50 mL/min; 8. left ventricular ejection fraction (LVEF) ≥ 50%; 12. ECOG Physical Status Score of 0-1 13. Expected survival ≥ 6 months 14. Subjects whose spouses are of childbearing age must agree to use contraception during the study and for 6 months after the last dose; sperm donation is not permitted during the study and for 6 months after the last dose 15. Ability to understand and sign an informed consent form. Exclusion Criteria: 1. Systemic chemotherapy, novel hormonal therapies, targeted therapies, immunotherapies, herbs with antitumour indications or other antitumour therapies (including 5-alpha reductase inhibitors, oestrogens, and medroxyprogesterone, etc.), with the exception of maintenance of castration therapies (LHRH agonists or LHRH antagonists) or treatments for bone metastases (e.g., denosumab, zoledronic acid), have been performed within the 4-week period prior to the administration of the first study drug (or the equivalent 5-half-life period of the drug, whichever is longer; the washout period for bicalutamide is 6 weeks). 2. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis (subjects who have been treated for brain metastases may be enrolled in this study provided they have stable disease \[no evidence of progression as determined by imaging for at least 4 weeks prior to study dosing and all neurological symptoms have returned to baseline levels\], there is no evidence of new or enlarging brain metastases, and discontinuation of steroid therapy at least 7 days prior to the first dose of the trial treatment. (This exception does not include carcinomatous meningitis, which should be excluded regardless of whether it is clinically stable or not). 3. Has received anti-HER2 therapy or any ADC therapy; 4. Subjects with a known mutation in the breast cancer susceptibility gene (BRCA) or ataxia telangiectasia mutated (ATM) gene (germline or somatic cell line); who are known to have a mutation in one of the above genes and had disease progression or intolerable toxicity on PARP inhibitor therapy are eligible; 5. Major surgery, systemic radiotherapy or biologic therapy within 4 weeks prior to first study drug administration, or minor surgery or local radiotherapy within 1 week prior to enrollment; 6. Participation in another clinical trial within 3 months prior to screening; 7. Toxicity due to prior antineoplastic therapy that has not recovered to Common Terminology Criteria for Adverse Events (CTCAE Version 5.0) Grade 1 or below, with the exception of alopecia and abnormalities in laboratory tests or toxicity associated with LHRH agonists or LHRH antagonists that are not considered by the investigator to pose a safety risk; 8. Known allergic reactions to components of the study treatment or its analogues 9. Diagnosis of other malignancies that are expected to affect life expectancy or may interfere with disease assessment. Except for cured non-melanoma skin cancer and superficial bladder cancer 10. Severe and/or persistent infection within 14 days prior to starting the study drug 11. Serum virological tests: positive HBsAg test result with a positive HBV DNA copy number; positive HCVAb test result; positive HIVAb test result; 12. Known serious cardiovascular disease, including any of the following: myocardial infarction, thrombotic event, or unstable angina pectoris in the past 3 months; chronic heart failure, New York Heart Association (NYHA) class II or higher; presence of unstable arrhythmia; uncontrolled hypertension; 13. Combined grade 2 and higher (CTCAE version 5.0) peripheral neuropathy 14. Presence of other systemic diseases that, in the judgement of the investigator, are not under stable control, including diabetes mellitus, liver cirrhosis, pneumonitis, and obstructive pulmonary disease; 15. In the judgement of the investigator, there were other circumstances that made participation in the study unsuitable.

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2024-04-30