A Study on the Safety and Efficacy of LAE001 in the Treatment of Metastatic Prostate Cancer

Exclusion Criteria

• •1. Patients who had been treated with abiraterone acetate or enzalutamide.
• •2. Phase I: Patients who received anti-tumor therapy such as chemotherapy, radiotherapy, targeted therapy, and endocrine therapy with androgen receptor inhibitors within four weeks prior to the first dose (the time from the last treatment with nitrosourea or mitomycin chemotherapeutic agents is \< 6 weeks, and the time from the last dose of bicalutamide or nilutamide is \< 6 weeks).
• •3. Phase II: Patients who received any chemotherapy, radiotherapy or surgery for metastatic prostate cancer before randomization. Exceptions: ADT therapy (LHRH agonist or orchiectomy) before Day 1 of Cycle 1. Or \>4 weeks since last use of bicalutamide or other generation antiandrogen receptor antagonist (please confirm with sponsor). Subjects may receive a course of palliative radiotherapy or surgery to treat symptoms caused by metastatic disease (e.g. spinal cord compression or obstruction), provided that it is administered at least 28 days prior to Day 1 of Cycle 1. All adverse events associated with such treatment must be alleviated to Grade 1 by Day 1 of Cycle 1.
• •4. Patients who underwent major surgery (major surgery refers to Grade 3 and Grade 4 surgery as defined in the "Administrative Measures for Clinical Application of Medical Technologies" promulgated on May 01, 2009) within 28 days before the study treatment, or who have not fully recovered from surgery (the investigator determines that the patient's participation in the clinical trial would pose a risk).
• •5. Patients with known severe cardiovascular diseases, including: myocardial infarction or thrombotic events in the past six months; unstable angina; heart failure of Class III or IV according to the criteria of the New York Heart Association (NYHA); QTc interval (QTcF) \> 450 ms during the screening visit; G3 hypertension that cannot be controlled even with standard treatment, systolic blood pressure \>160 mmHg or diastolic blood pressure\>100 mmHg).
• •6. Patient who have not yet recovered from the toxicity of the former treatment regimen before drug administration on Day 1 of Cycle 1, and still have toxic reactions (excluding hair loss) above Grade 1 according to the grading scale of version 5.0 of the Common Terminology Criteria for Adverse Events (CTCAE).
• •7. Patients with clinically obvious gastrointestinal abnormalities that may affect the intake, transportation or absorption of drugs (such as patients who are unable to swallow, have chronic diarrhea or intestinal obstruction, or who had undergone total gastrectomy).
• •8. Patients with visceral metastasis involving the adrenal glands and central nervous system.
• •9. Patients with evidence of myelosuppression, and hydronephrosis in both kidneys as well as bladder neck obstruction that affects kidney function
• •10. Type I diabetes and type II diabetes that cannot be controlled by medication
• •11. Patients with a history of severe central nervous system diseases, including epilepsy.
• •12. Patients who had other malignant tumors (except for basal or squamous cell carcinoma) in addition to prostate cancer in the past five years, which are currently clinically significant and require intervention.
• •13. Patients who received 5α-reductase inhibitors (finasteride, dutasteride), estrogen, cyproterone and other drugs for treatment within four weeks before the first dose, and whose period of drug discontinuation has not exceeded five half-lives of the corresponding drugs; the drugs must have been discontinued for more than two weeks if the half-life is unknown.
• •14. Male patients whose sexual partners are women of childbearing age, where the patient and / or his sexual partner do not agree to use highly effective contraceptive measures (i.e. contraceptives with a low failure rate (less than or equivalent to 1% per year) when used consistently and correctly), and continued use of such measures until four weeks after drug discontinuation.
• •15. Patients who require systemic steroids or who had received systemic steroids (more than or equivalent to 10 mg of prednisone per day) 30 days before enrollment; topical, inhaled, ophthalmic or intra-articular medications are acceptable.
• •16. Patients who need to take diuretics (non-potassium-sparing).
• •17. Patients known to have pituitary or adrenal insufficiency.
• •18. Patients with known congenital or acquired immunodeficiency, active tuberculosis, etc.
• •19. Patients with active infection(s) that require systemic treatment within 10 days prior to signing the informed consent form.
• •20. Chronic hepatitis B carriers with untreated chronic active hepatitis B or with HBV DNA ≥ 1000 copies/mL (or ≥ 200 IU/mL), or patients with active hepatitis C.
• •21 The patient is currently receiving the following drugs and cannot discontinue the drugs at least one week before starting the study drug: Spironolactone Substrates of CYP1A2, CYP2E1 or CYP2C19, with a narrow therapeutic index Strong inhibitor or strong inducer of CYP1A2 Strong inhibitor of BSEP Grapefruit juice, and herbs such as St. John's wort, kava, ephedra, ginkgo biloba leaves, dehydroepiandrosterone, yohimbine, saw palmetto, and ginseng.
• •22\. The patient is currently receiving a moderate or strong inhibitor or isoenzyme inducer of CYP3A. Patients taking strong inducers need to discontinue the drug for at least one week, and patients taking strong inhibitors need to at least discontinue the drug before receiving the study treatment.
• •23\. Patients with other physical, psychological or social problems, including drug abuse, or who are deemed by the investigator to be unsuitable for participation in this study.