Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer

Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer: an Open-label, Multi-center, Dose-escalating，Phase I/Ib Study.

This study is a multi-center, open-label, dose-esclation I/Ib clinical study to explore safety, efficacy an pharmacokinetics of proxalutamide in patients with metastatic breast cancer.

This study includes two stages, stage I: single- and multiple-dose tolerance and pharmacokinetic study; stage 2: preliminary efficacy and safety study.

This study is a multi-center, open-label, dose-esclation study.

Subjects will be enrolled to the 100mg, 200mg, 300mg, 400mg and 500mg group in turn. Unless DLT was found, the dose esclation will continue. 28 days of DLT observation period is needed after 7-day single dose administration, until disease progression, intolerable toxicities (AEs), or withdrawn consent.

After the completion of stage 1, 2 doses for the stage 2 will be determined. In stage 2, patients with AR-positive metastatic breast cancer will be selected to explore the efficacy and safety of proxalutamide, and biomarkers will be explored.

Inclusion Criteria:

1. Age ≥18 years female;

2. Stage 1:Histology or cytology confirmed metastatic breast cancer, first-line chemotherapy or targeted therapy failure or intolerance

   Stage 2: Histological or cytological confirmed metastatic breast cancer patients who failed or intolerant to anti-tumor therapy; have a positive AR test result;

3. At least one measurable lesion based on RECIST version 1.1 ;

4. ECOG performance status: 0-1;

5. Have a predicted life expectancy of greater than 3 months;

6. The functions of the important organs are confirmed with the following requirement:

   • Hemoglobin (HGB) ≥ 90 g/L(no blood transfusion within 14 days );
   • Absolute neutrophil count (ANC) ≥ 1.5×10^9/L；
   • Platelets (PLT) ≥ 100×10^9/L(If the coagulation function is normal,Platelets (PLT) ≥ 75×10^9/L )；
   • Total bilirubin (TBIL) ≤ 1.5× Upper limit of normal value (ULN) -Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine -
   • Aminotransferase (ALT) ≤2.5× ULN

7. Understand and voluntarily sign the informed consent form；

8. Subject is willing and able to comply with all protocol required visits and assessments；

Exclusion Criteria:

1. Pregnant, lactating women, or those who have fertility and are reluctant to take effective contraceptive measures;
2. Prior chemotherapy, radiation, targeted therapy ,androgen receptor inhibitors therapy (abiraterone,enzalutamide,etc )，other endocrine therapy ，and has acceptted traditional chinese herbal medicine treatment less than 4 weeks prior to the start of study medication.
3. Has severe cardiovascular disease
4. The toxicity of the previous treatment plan has not been restored before enrollment, and there is still non-hematologic toxicity of grade 1 or above (except for hair loss)
5. Known gastrointestinal disease or condition that affects the absorption of GT0918;
6. Known or suspected brain metastases, including the central nervous system and spinal cord compression or meningeal metastasis;
7. History of severe central nervous system diseases (including patients with epilepsy);
8. Known hypersensitivity to proxalutmide or its excipients.
9. Participated in clinical trials of other drugs or medical devices within one month prior to screening, or plan to participate in any other clinical trials during the study period;
10. Subjects with any other serious disease considered by the investigator not in the condition to enter into the trial;