Phase I Study of HSK46575 in Patients With Metastatic Castration-Resistant Prostate Cancer

Prior treatment

• Subjects who have received any antitumor therapy within 4 weeks (or 5 half-lives, whichever is shorter) prior to the first dose; or treatment with nitrosoureas, bicalutamide, or nilutamide within 6 weeks (or 5 half-lives, whichever is shorter) prior to the first dose;
• Subjects whose toxicity from prior anticancer therapy remains \> Grade 1 before the first dose;
• Subjects who have used strong or moderate CYP3A4 inhibitors or inducers, CYP2C9 sensitive substrates, and OCT2 or MATE1 substrates within 14 days or 5 half-lives prior to the first dose of the investigational drug, whichever is longer;
• Subjects who have undergone Grade 3-4 surgery;
• Subjects who plan to receive any other antitumor therapy during the study ;
• Within 6 months before the first dose, subjects had concurrent pituitary or adrenal dysfunction;
• Subjects with active cardiac disease within 6 months prior to the first dose, or a history of arterial or venous thromboembolism;
• Subjects who have participated in other clinical studies within 4 weeks before the first dose;

Other illness

• Subjects with known hypersensitivity to the active ingredient or excipients of HSK46575 Tablets;
• Subjects with serious bone damage caused by prostate cancer bone metastasis as assessed by the investigators;
• Subjects with uncontrolled hypertension;
• Subjects with central nervous system disorders such as epilepsy and multiple sclerosis;
• Subjects with a history of other malignancies;
• Subjects with a history of immunodeficiency;
• Subjects with active HBV, HCV, or syphilis infection;
• Other conditions.

Lab values

• Subjects with a QTc interval prolongation to \>470 ms during the screening period calculated by the Fridericia formula；

Other

• Subjects with active metastases to central nervous system;

• Male, aged ≥18 years;
• ECOG (Eastern Cooperative Oncology Group) 0-1, expected survival of ≥ 3 months;
• Histology or cytology confirmed adenocarcinoma of the prostate;
• Radiological evidence of metastatic bone or soft tissue lesions;
• Ongoing medical castration or previous surgical castration;
• Testosterone at castration level during screening;
• Prior to screening, subjects with evidence of disease progression while receiving ADT (androgen deprivation therapy);
• Had progressed on at least one novel endocrine therapy, and had progressed on at least one taxane-based chemotherapy (or those who are intolerant or refuse chemotherapy);
• The functional level of organs must meet the requirements.