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

Study Overview
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Brief Summary
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A Multicenter Open-label Non-comparative 2-Stage Phase 1a/1b Study to Assess the Safety and Pharmacokinetics of Oral BCD-115 (JSC BIOCAD, Russia) in Combination with Endocrine Therapy in Women with ER(+) HER2(-) Local Advanced and Metastatic Breast Cancer

Detailed Description
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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.

Official Title
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A Multicenter Open-label Non-comparative 2-Stage Phase 1a/1b Study to Assess the Safety and Pharmacokinetics of BCD-115 (JSC BIOCAD, Russia) in Combination With Endocrine Therapy in Women With ER(+) HER2(-) Local Advanced and Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: BCD-115


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: BCD-115 in dose escalation regimen<br>BCD-115 will be 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. | Drug: BCD-115<br>* Inhibitor of CDK8/19<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC0-t) | To determine AUC0-t after single doses of BCD-115 p.o. administration with dose escalation; | 90 days | 
| Peak Plasma Concentration (Cmax) | To determine observed maximum concentration in plasma or serums after single doses of BCD-115 p.o. administration with dose | 90 days | 
| The incidence and severity of AEs | The incidence and severity of AEs (%) related with the therapy based on results of review by 3 experts (%) | 90 days | 
| The incidence of grade 3-4 AEs | The incidence of grade 3-4 AEs (%) related with the therapy based on results of review by 3 experts | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment discontinuation due to adverse events | Treatment discontinuation due to adverse events (%) | 90 days |