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

The goal of this clinical trial is to learn if tinengotinib combined with darolutamide or enzalutamide works to treat participants with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior androgen receptor pathway inhibitors (ARPIs). It will also learn about the safety of the combination therapy. The main questions it aims to answer are: 1. If participants with mCRPC can benefit from the combination therapy of tinengotinib plus one ARPI? 2. What medical problems do participants have when taking the combination therapy? Participants will take tinengotinib with darolutamide or enzalutamide to find the optimal dose and regimen of tinengotinib for the combination therapy in stage A. In stage B, participants will take preferred combination regimen of tinengotinib plus darolutamide/enzalutamide identified in stage A. In stage C, researchers will compare selected combination therapy versus standard treatment and/or monotherapy to see if the combination therapy works better.

Inclusion Criteria: 1. Male aged \>= 18 years at the time of signing the informed consent form (ICF). 2. 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). 3. Baseline imaging confirming metastatic lesions in bone (\>=2 bone lesions) or soft tissue; lesions identified only by PET imaging are not acceptable. 4. 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. 5. 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. 6. Disease failure after \