Study of BCD-115 in Women With ER(+) HER2(-) Local Advanced and Metastatic Breast Cancer

Multicentre dose-finding open-label non-comparative phase Ia/Ib clinical trial for investigation of the safety, tolerability, pharmacokinetics of BCD-115 administered p.o. with intrapatient dose escalation in the population of patients with ER(+) HER2(-) advanced breast cancer in combination with a standard dose of endocrine therapy.

The trial will be conducted in two stages:

Stage 1 - finding of the maximum tolerated dose, determination of the recommended dose for Stage 2.

Stage 2 - study of the recommended dose from Stage 1 of BCD-115, analysis of tolerability and safety of selected dose/doses in additional cohorts, and determination of the estimated therapeutic dose/doses for further clinical studies.

Inclusion criteria

• Written informed consent and ability to follow the Protocol procedures;
• Age ≥18 years;
• Female gender;
• Postmenopausal status (Prior bilateral surgical oophorectomy; or medically confirmed post-menopausal status defined as spontaneous cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause);
• Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease;
• Progression of advanced breast cancer on first line endocrine therapy for advanced breast cancer.
• ER positive tumor ≥ 10%;
• HER2 negative breast cancer by FISH or IHC;
• Eastern Cooperative Oncology Group (ECOG) performance status 0 -2
• Measurable disease according to RECIST 1.1 (only bone disease is not allowed)
• Resolution of all acute toxic effects of prior therapy (including endocrine therapy) or surgical procedures to CTCAE grade ≤1
• Adequate organ function;
• Life expectancy - 12 weeks or more from the moment of randomization

Exclusion criteria

• HER2-positive tumour ;
• Patients with unstable brain metastases, advanced, symptomatic, visceral spread disease, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions pleural, pericardial, peritoneal, pulmonary lymphangitis, and over 50% liver involvement).
• Important cardiovascular events in the past 6 months to randomization;
• GI diseases which may affect the absorption of the study drug;
• Inadequate hematopoietic function: neutrophils ≤1500/mm3, platelets ≤100 000/mm3,or hemoglobin ≤90 g/L;
• Inadequate renal function: creatinine level ≥ 1.5 × upper limit of normal (ULN);
• Inadequate liver function: bilirubin level ≥ 1.5 × ULN, AST and ALT levels ≥ 2.5 × ULN (5 × ULN for patients with liver metastases), alkaline phosphatase level ≥ 5 × ULN;
• Concurrent antitumor treatment 21 days before randomization (surgery, radiation therapy; chemotherapy, except endocrine therapy);
• Any other concomitant cancer including contralateral breast cancer revealed within 5 years prior to screening, except curatively treated intraductal carcinoma in situ, curatively treated cervical carcinoma in situ or curatively treated basal cell or squamous cell carcinoma;
• Conditions limiting patient's adherence to protocol requirements (dementia, neurologic or psychiatric disorders, drug addiction, alcoholism and others);
• Concomitant participation in other clinical trials, previous participation in other clinical trials within 30 days before entering into the trial, previous participation in the same trial;
• Acute or active chronic infections;
• HCV, HBV, HIV or syphilis infections;
• Obstacles to p.o. administration of study drug.