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

Summary

This is a phase I, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, PK（pharmacokinetics） and PD（pharmacodynamics） of HSK46575 when given orally in patients with metastatic castration-resistant prostate cancer.

Eligibility

Inclusion Criteria:

1. Male, aged ≥18 years;
2. ECOG (Eastern Cooperative Oncology Group) 0-1, expected survival of ≥ 3 months;
3. Histology or cytology confirmed adenocarcinoma of the prostate;
4. Radiological evidence of metastatic bone or soft tissue lesions;
5. Ongoing medical castration or previous surgical castration;
6. Testosterone at castration level during screening;
7. Prior to screening, subjects with evidence of disease progression while receiving ADT (androgen deprivation therapy);
8. 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);
9. The functional level of organs must meet the requirements.

Exclusion Criteria:

1. Subjects with known hypersensitivity to the active ingredient or excipients of HSK46575 Tablets;
2. 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;
3. Subjects whose toxicity from prior anticancer therapy remains \> Grade 1 before the first dose;
4. 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;
5. Subjects who have undergone Grade 3-4 surgery;
6. Subjects who plan to receive any other antitumor therapy during the study ;
7. Subjects with active metastases to central nervous system;
8. Subjects with serious bone damage caused by prostate cancer bone metastasis as assessed by the investigators;
9. Within 6 months before the first dose, subjects had concurrent pituitary or adrenal dysfunction;
10. Subjects with uncontrolled hypertension;
11. Subjects with central nervous system disorders such as epilepsy and multiple sclerosis;
12. Subjects with active cardiac disease within 6 months prior to the first dose, or a history of arterial or venous thromboembolism;
13. Subjects with a QTc interval prolongation to \>470 ms during the screening period calculated by the Fridericia formula；
14. Subjects with a history of other malignancies;
15. Subjects with a history of immunodeficiency;
16. Subjects with active HBV, HCV, or syphilis infection;
17. Subjects who have participated in other clinical studies within 4 weeks before the first dose;
18. Other conditions.

Conditions2

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