Breast Cancer Clinical Trials

• Have given written informed consent prior to any study specific procedures.

• Male or female, aged ≥18 years.

• Subjects with advanced solid tumors:

‣ Phase 1: Histologically or cytologically confirmed, locally advanced (not amenable to curative treatment of surgical resection or radiation therapy), recurrent, or metastatic solid tumors that were refractory to standard therapy or for which no standard-of-care therapy.

⁃ Phase 2a Cohort A: HR+/HER2- locally advanced, recurrent, or metastatic breast cancer with disease progression after first-line endocrine therapy (not fulvestrant) or intolerant of it, histologically confirmed by the primary and/or metastatic lesions, not amenable to chemotherapy or curative treatment of surgical resection or radiation therapy; if the pathology of the primary and metastatic lesions are inconsistent, diagnosis should be based on metastatic lesions' pathology.

⁃ Phase 2a Cohort B: HR+/HER2- locally advanced, recurrent, or metastatic breast cancer with no prior systemic therapy in this disease setting or relapse more than 1 years from completion of adjuvant endocrine therapy, histologically confirmed by the primary and/or metastatic lesions, not amenable to chemotherapy or curative treatment of surgical resection or radiation therapy; if the pathology of the primary and metastatic lesions are inconsistent, diagnosis should be based on metastatic lesions' pathology.

⁃ Female patients with breast cancer at Phase IIa must also meet the following criteria:

‣ (1) Postmenopausal patients must meet at least one of the following criteria:

• Age ≥ 60 years old;

• Patients \< 60 years of age who have menstruation ceased for at least 12 consecutive months and have not received chemotherapy, tamoxifen, toremifene or ovarian function inhibitors, and have blood estrogen and FSH levels within the reference range for postmenopausal women;

• Previous bilateral ovariectomy;

• Patients \< 60 years of age who are being treated with tamoxifen or toremifene with blood estrogen and FSH levels within the reference range for postmenopausal women.

‣ (2) Premenopausal/perimenopausal patients must meet the following criteria: Premenopausal/perimenopausal patients requiring ovarian function suppression must start treatment at least 4 weeks prior to enrollment and the treatment should be maintained during the trial.

• At least 1 measurable lesion based on the RECIST v1.1 criteria.

• Life expectancy≥ 12 weeks.

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)≤1.

• Adequate bone marrow and organ function, defined as following:

∙ absolute neutrophil count≥1.5×10\^9/L, platelets≥100×10\^9/L, hemoglobin≥100 g/L;

‣ total bilirubin≤1.5×ULN(≤3×ULN for Gilbert syndrome), alanine aminotransferase and aspartate aminotransferase≤3×ULN;

‣ serum creatinine≤1.5×ULN or a creatinine clearance calculated by Cockcroft-Gault formula≥50 mL/min; urinary protein measured by semi-quantitative method\<2+; if urinary protein measured by semi-quantitative method at baseline ≥2+, 24-h urinary protein\<1g;

‣ activated partial thromboplastin time and international normalized ratio≤1.5×ULN;

‣ LVEF≥50%;

‣ Corrected QT interval (QTcF)\<450ms for men and \<470ms for women at resting.

• Female subjects should take effective contraceptive methods during the study and for 60 days after the last dose of BPI-1178, and must have a negative pregnancy test prior to dosing if of child-bearing potential, or must have evidence of non-child-bearing potential; male subjects should take effective contraceptive methods during the study and for 120 days after the last dose of BPI-1178.

• All subjects must have enough mental behavior ability, understand the nature and significance of the study, as well as the risks associated with the study.