Safety, Efficacy and Pharmacokinetics of TT00420 Tablets Combined With Novel Endocrine Therapy in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC)

Korábbi kezelés

• Prior treatment with tyrosine kinase inhibitors (TKIs).
• Prior treatment with darolutamide or enzalutamide (except for treatment duration <= 1 month).
• Concurrent central nervous system (CNS) metastases with radiological or symptomatic progression within 28 days prior to study treatment initiation.
• Concurrent other malignancies requiring active treatment. Malignancies not requiring treatment within 5 years and cured localized tumors such as basal cell carcinoma of the skin, papillary thyroid carcinoma, etc., are excluded from this criterion.
• Prior administration of other anti-tumor therapies within <=5 half-lives or 14 days (whichever is shorter) before initiation of study treatment, or failure to recover from adverse events of prior therapy (except for adverse events <= Grade 1 or <= Grade 2 adverse events judged by the investigator not to pose a safety risk). Sex hormone therapies other than LHRH agents must be discontinued >=7 days before study drug administration.
• Receipt of extensive radiotherapy within 4 weeks prior to study treatment initiation, or palliative local radiotherapy within 2 weeks, or failure to recover from adverse events of prior therapy. (If the investigator considers that early initiation of study drug is in the participant's best interest based on benefit-risk assessment, study drug treatment may be started during the washout period upon sponsor approval.)
• Major surgery within 4 weeks prior to study treatment initiation, or failure to recover from surgical adverse events (except for adverse events <= Grade 1 or <= Grade 2 adverse events judged by the investigator not to pose a safety risk). 9. History of severe cardiovascular or cerebrovascular diseases.
• Use of strong CYP3A4 inhibitors and other agents that may affect the metabolism of the study drug within <=2 weeks or 5 half-lives (whichever is shorter) prior to study treatment initiation. Other agents that may affect the concomitant medications are as follows: (1) Participants receiving enzalutamide combination therapy: use of strong CYP2C8 inhibitors; (2) Participants receiving darolutamide combination therapy: use of rosuvastatin, strong P-gp inhibitors and inducers.

Más betegség

• Uncontrolled hypertension (systolic blood pressure >=150 mmHg or diastolic blood pressure >=100 mmHg; repeat measurement is permitted after an interval of >=10 minutes if abnormal), or a medical history of hypertensive crisis/hypertensive encephalopathy. Uncontrolled is defined as failure to achieve blood pressure control despite antihypertensive therapy with stable type/dose for at least 1 week.
• Severe gastrointestinal disease or gastrointestinal dysfunction that may alter the absorption, metabolism or excretion of the study drug; eligibility will be determined by investigator assessment (including but not limited to total gastrectomy, short bowel syndrome, etc.).
• Positive human immunodeficiency virus (HIV) test. 14. Active HBV infection (abnormal HBV serology other than positive hepatitis B surface antibody; HBV DNA copy number testing is required to confirm activity) and/or HCV infection (HCV RNA copy number testing is required to confirm activity if HCV antibody is positive).
• Inability to swallow or tolerate oral medication. 16. Other conditions judged by the investigator to make the participant unsuitable for study participation.

Laborértékek

• Bleeding disorders, thrombotic disorders, or therapeutic anticoagulation requiring INR monitoring, such as warfarin or any other coumarin derivative anticoagulants.

• Male aged >= 18 years at the time of signing the informed consent form (ICF).
• Histologically or cytologically confirmed prostate adenocarcinoma; neuroendocrine differentiation after prior treatment is permitted (patients with de novo neuroendocrine prostate cancer at initial diagnosis are excluded).
• Baseline imaging confirming metastatic lesions in bone (>=2 bone lesions) or soft tissue; lesions identified only by PET imaging are not acceptable.
• Receipt of continuous medical castration for >=90 days or prior surgical castration, with serum testosterone < 50 ng/dL (1.73 nmol/L) within 28 days prior to the first dose. Participants receiving medical castration with a luteinizing hormone-releasing hormone (LHRH) analogue must continue treatment throughout the study.
• Documented disease progression (per RECIST v1.1 and/or PCWG3) after >1 month of prior novel endocrine therapy (including abiraterone and AR inhibitors).
  • Cohort B: Prior exposure to only one type of novel endocrine therapy.
• Disease failure after <=1 line of chemotherapy administered during the castration-resistant phase (chemotherapy duration <=1 month and ADC agents are not counted as systemic chemotherapy).
• ECOG performance status <= 1.
• Adequate organ and bone marrow function (no hematopoietic growth factors, blood transfusion or related blood products within 14 days before the first dose).
• Must agree not to donate sperm or cryopreserve sperm for future assisted reproduction during study treatment and for 3 months after the last dose of study treatment. If the participant is spermatogenic and his female partner is of childbearing potential, highly effective contraception must be used.
• Able to provide informed consent and comply with study procedures.