Phase I Study of BEBT-209 in Women With Advanced Breast Cancer

Inclusion Criteria

• •1. Age: ≥18 years old;
• •2. Confirmed HR +/HER2- breast cancer in women with evidence of focal recurrence or metastasis not amenable to curative surgical resection or radiation therapy.
• •3. Menstrual status:
• •3.1 Subjects enrolled in the dose escalation phase, Phase Ib combined with letrozole, combined with fulvestrant first-line therapy were required to be female patients who achieved menopausal status or were treated with LHRH agonists; 3.2 Subjects enrolled in Phase Ib monotherapy and combined fulvestrant second-line/third-line therapy are required to be postmenopausal, premenopausal/ perimenopausal, and amenorrheic women;
• •Menopausal status(note 2) is defined as having met any of the following:
• •* Prior bilateral oophorectomy;
• •* Age≥ 60 years old
• •* Age \< 60 years, Spontaneous amenorrhea ≥ 12 months and blood follicle-stimulating hormone (FSH) and estradiol (E2) levels within the postmenopausal range (in conjunction with reference ranges at each site) in the absence of chemotherapy, tamoxifen, toremifene, or ovarian castration within the past year;
• •* Patients \< 60 years of age who were taking tamoxifen or toremifene had blood follicle-stimulating hormone (FSH) and estradiol (E2) levels within the postmenopausal range on two consecutive occasions (in conjunction with reference ranges at each site);
• •4. Prior Therapy( Note 3):
• •4.1 Patients who have failed standard therapy or for whom standard therapy is not applicable are required for the dose escalation phase; 4.2 Phase IB monotherapy group: patients who have previously failed antiestrogen therapy and received at least 1 chemotherapy regimen; 4.3 The stage IB combined letrozole group required no previous first-line treatment for focal recurrent or metastatic ER + breast cancer; 4.4 Prior therapy in the Stage IB combined fulvestrant arm must have met one of the following: 4.4.1 Premenopausal/perimenopausal/postmenopausal patients can be enrolled, and premenopausal/perimenopausal patients are required to use luteinizing hormone-releasing hormone (LHRH agonist) at the same time; 4.4.2 Progression confirmed by imaging during or within 12 months after discontinuation of adjuvant endocrine therapy (AI or TAM); 4.4.3 Progression confirmed by imaging during or within one month after discontinuation of endocrine therapy for the first recurrence and metastasis; 4.4.4 Patients in the relapse or metastatic stage are allowed to receive no more than one line of chemotherapy in addition to endocrine therapy.
• •Note 3: The number of lines of therapy and corresponding menstrual status definitions refer to the Ribociclib Phase 3 Clinical Study (NCT02422615), the abemaciclib Phase 2 Clinical Study (Clin Cancer Res. 2017 September 01; 23 (17): 5218 - 5224), and the Palbociclib in Combination with Fulvestrant Clinical Study (NCT02738866).
• •5. Measurable lesions as defined by RECIST V.1.1 or osteolytic bone metastases only as judged by the investigator based on clinical presentation. Tumor lesions previously treated with radiotherapy or other local therapy were considered measurable only if disease progression at the treatment site was clearly documented after completion of treatment.
• •6. ECOG score of 0-2.
• •7. Have adequate organ and bone marrow function, defined as follows: ANC≥1,500/mm\^3（1.5 x 10\^9 /L）； Platelet ≥ 100,000/mm\^3 (100 x10
• •\^9 /L）； hemoglobin≥ 9 g/dL (90 g/L); Both ALT or AST ≤ 2.5×ULN, and ALT or AST ≤ 5.0×ULN in liver metastasis; Total bilirubin (TBIL) ≤ 1.5×ULN, 3.0×≤ULN in liver metastasis; Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 60 mL/min (according to the Cockcroft and Gault formula).
• •8. Resolution of all acute toxicities from prior anticancer therapy or surgical procedures to baseline severity or NCICTCAE version 5.0 ≤ Grade 1 (except alopecia or other toxicities that, in the opinion of the investigator, pose no safety risk to the patient).
• •9. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to starting study drug and be willing to use a medically recognized highly effective form of birth control (eg, intrauterine device, contraceptive pill, or condom) during the study and for 1 month after the last dose of study drug.
• •10. Willing to sign the informed consent form after thorough understanding.