Prostate cancer
Conditions
Interventions
Dose escalation group:The initial dose of SHR-4394 was 1.6 mg/kg and was administered intravenously every 3 weeks (Q3W) for a treatment cycle of 21 days. The BOIN design was used for dose escalation,
Dose extension group:According to the safety, tolerability, PK and other data of different dose groups in the dose escalation stage, 2~3 dose groups were selected for dose extension. The plan is to ex
Therapeutic extension group:Patients with advanced mCRPC are
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Inclusion criteria
Inclusion criteria: Participants must meet all of the following criteria to enter the study: 1) Age 18-85 years old, male; 2) ECOG score of physical condition 0 ~ 1; 3) Expected survival =6 months; 4) Prostate adenocarcinoma confirmed by histology or cytology and not suggestive of neuroendocrine or small cell features; 5) Imaging examination with evaluable criteria (according to PCWG3, imaging examination with evaluable criteria refers to examination with a specific standard method for evaluating the lesion, including CT, MRI or bone scan) demonstrating the presence of metastatic lesions; 6) Patients with metastatic prostate cancer who had disease progression while undergoing castration at the time of enrollment had at least one of the following three events: (1) PSA progression, including progression to CRPC (defined as PSA > 1 ng/mL at least 1 week interval and PSA > 50% higher than baseline for 2 consecutive times) in HSPC treatment and PSA progression in CRPC treatment (see PSA progression criteria in 8.2 Effectiveness Evaluation and Step-by-step PSA Evaluation); Soft tissue lesion progression: disease progression as defined in RECIST 1.1; Progression of bone lesions: Progression of bone diseases defined by PCWG3 criteria, that is, =2 or more new lesions found on bone scans; 7) Ongoing luteinizing hormone releasing hormone analogue (LHRHa) therapy (drug castration) or prior bilateral orchiectomy (surgical castration); Participants who did not undergo bilateral orchiectomy must maintain effective LHRHa therapy throughout the study period; 8) At screening, testosterone was at castration level (< 50 ng/dL or 1.7nmol/L); 9) Failure of treatment with at least one new endocrine drug (such as abiraterone, Enzalutamide, etc.) in the past (disease progression occurs during treatment; The definition of disease progression is the same as the inclusion criteria (6)), and treatment with at least one taxoid chemotherapy agent has failed/is unable to tolerate or refuse chemotherapy; 10) The functional level of the organ must meet the following requirements: • Blood routine examination (no blood transfusion or blood products within 14 days before the first dose, no correction with G-CSF or other hematopoietic stimulating factors) : absolute neutrophil count (ANC) =1.5×109/L; Platelet count (PLT) =100×109/L; Hemoglobin (Hb) =90 g/L; • Liver function test: total bilirubin (TBIL) <=1.5× upper limit of normal (ULN) (<=2×ULN if liver metastases); Serum aminotransferase ALT and/or AST <=3×ULN (<=5×ULN in case of liver metastasis); • Renal function test: serum creatinine (Cr) <=1.5×ULN; Urinary protein <2+; If the urinary protein is =2+, it should be confirmed that the 24-hour urinary protein amount is <=1.0g; Electrocardiogram: Fridericia formula corrects QT interval (QTcF) to be normal (male <=470 ms); • Heart color ultrasonography: left ventricular ejection fraction (LVEF) =50%; • Coagulation function test: APTT<=1.5×ULN, INR or PT<=1.5×ULN. 11) Male subjects must agree to take highly effective contraception with their partner from signing the informed consent until 6 months after the final administration of the experimental drug, and are prohibited from donating sperm; 12) Voluntarily participate in this clinical trial, understand the research procedure and have signed informed consent.
Exclusion criteria
Exclusion criteria: 1) Plan to receive any other anti-tumor therapy during this trial; 2) Received other investigational drugs or treatments that are not on the market within the 4 weeks prior to the first dose of the study; 3) Systemic anti-tumor therapy, including chemotherapy, targeted therapy, immunotherapy, attenuated active vaccination, radiotherapy, etc., was received 4 weeks before treatment in the first study (for small molecule targeted drugs, the washout period was 7 days or 5 times the drug half-life, whichever was longer; The washout period of bicalutamide was 6 weeks. Anti-tumor Chinese medicine or proprietary Chinese medicine, eluting period is 14 days); 4) Have previously received antiboy-coupled drug therapy with one of the following characteristics: target PSMA or topoisomerase I inhibitor components, such as ARX-517, Lu-177 labeled PSMA, Enhertu (DS-8201a), etc.; 5) Surgical procedures requiring tracheal intubation and general anesthesia were performed within 28 days prior to the initial study, diagnostic or superficial surgery was performed within 7 days prior to the initial study, or elective surgery was expected during the trial period; 6) Received CYP3A4, CYP2D6 strong depressant or strong inducer, P-gp inhibitor treatment within 5 half-lives before the first medication; 7) According to NCI-CTCAE v5.0, adverse events caused by previous antitumor therapy did not return to <= grade 1 (except grade 2 peripheral neuropathy, alopecia, hypothyroidism controlled by hormone replacement therapy, and type 1 diabetes well controlled by insulin); 8) Known to be allergic to any component of SHR-4394 product (antibody-coupled toxin, antibody, toxin 9106-IM-2), or to humanized monoclonal antibody products; 9) inadequately treated central nervous system (CNS) metastases, or the presence of uncontrolled or symptomatic active CNS metastases. Patients with CNS metastasis who have been adequately treated and whose neurological symptoms have returned to disappearance/resolution at least 4 weeks prior to randomization (except for residual signs or symptoms associated with CNS treatment) may be enrolled in the study. In addition, participants must discontinue corticosteroids or receive prednisone (or an equivalent dose of another corticosteroid) at least 4 weeks prior to the first dose of the study; 10) Patients with uncontrolled tumor-related pain as judged by the investigator. Participants requiring pain medication must already have a stable pain treatment regimen when they enter the study; 11) Third space effusion such as pleural effusion, pericardial effusion, or abdominal effusion which can not be controlled by treatment such as puncture drainage within 28 days before the first administration, or relapse rapidly after puncture drainage, requiring repeated drainage; 12) Any other malignancy within 5 years prior to initial administration, except for adequately treated basal cell or squamous cell skin cancer, papillary thyroid carcinoma after radical surgery, and ductal carcinoma in situ after radical surgery; 13) Patients with interstitial pneumonia or interstitial lung disease, or a prior history of interstitial pneumonia or interstitial lung disease requiring hormone therapy, or other pulmonary fibrosis, persistent pneumonia, drug or radiotherapy-induced pneumonia, a history of congenital pneumonia, or any evidence of active pneumonia found on chest CT scan that may interfere with the judgment of immune-related pulmonary toxicity; 14) Active and sever
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics;immunogenicity; | — |
Countries
China
Contacts
Public ContactWei Qiang/Dong Qiang/Feng Ping
West China Hospital of Sichuan University
Outcome results
None listed