Clinical Study of the Efficacy and Safety of BCD-178 and Perjeta® as Neoadjuvant Therapy of HER2-Positive Breast Cancer

Study Overview
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Brief Summary
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The goal of this study is to compare the efficacy and safety of BCD-178 and Perjeta as neoadjuvant therapy for HER2-positive breast cancer. Subjects with histologically confirmed diagnosis of HER2-positive invasive breast cancer (stage II-III, tumor size > 2 cm), with no estrogen (ER) and progesterone (PR) receptors will be randomized to one of two treatment groups (BCD-178 group or Perjeta group) in a 1:1 ratio.

Official Title
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A Double-Blind, Randomized Clinical Study of the Efficacy and Safety of BCD-178 and Perjeta® as Neoadjuvant Therapy of HER2-Positive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: BCD-178
* Drug: Perjeta


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent ; Histologically confirmed diagnosis of invasive breast cancer; Disease stage cT2-cT4, cN0-cN3, cM0; Positive HER2 expression, negative estrogen and progesterone receptor expression; ECOG score 0-1; Adequate organ function; Baseline LVEF ≥ 55%, as measured with the standard procedure; Consent of women of childbearing potential to use highly effective methods of contraception, starting from the signing of the informed consent form, throughout the study and for 6 months after receiving the last dose of the product. Exclusion Criteria: Stage IV (metastatic) breast cancer; A history of any systemic therapy for breast cancer; Concomitant diseases and/or conditions that significantly increase the risk of adverse events during the study; Pregnancy or breastfeeding, as well as pregnancy planning throughout the study and for 6 months after receiving the last dose of the product; Hypersensitivity or allergy to any of the components of BCD-178, Perjeta, trastuzumab, carboplatin, and docetaxel.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-178 group<br>Neoadjuvant therapy stage (6 cycles, 18 weeks): BCD-178, Trastuzumab, Docetaxel, Carboplatin; Surgical treatment; Adjuvant therapy stage (up to 12 months of HER2-targeted therapy in total): BCD-178, Trastuzumab | Drug: BCD-178<br>* at an initial dose of 840 mg (1 cycle), then 420 mg<br>* Other names: pertuzumab;|
| Active Comparator: Perjeta Group<br>Neoadjuvant therapy stage (6 cycles, 18 weeks): Perjeta, Trastuzumab, Docetaxel, Carboplatin; Surgical treatment; Adjuvant therapy stage (up to 12 months of HER2-targeted therapy in total): BCD-178, Trastuzumab | Drug: Perjeta<br>* at an initial dose of 840 mg (1 cycle), then 420 mg<br>* Other names: pertuzumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the efficacy of BCD-178 and Perjeta as neoadjuvant therapy by studying the total pathological complete response (tpCR) rate | Proportion of subjects achieving tpCR | immediately after the surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| breast pathological complete response (bpCR) rate | Proportion of subjects achieving bpCR; | immediately after the surgery | 
| overall response rate (ORR) | the ORR according to RECIST 1.1 criteria | at Week 18 | 
| breast-conserving surgery rate | Proportion of subjects with breast-conserving surgery | immediately after surgery | 
| safety assessment | Proportion of subjects with adverse reactions; Proportion of subjects with CTCAE 5.0 grade 3 or higher adverse reactions; • Proportion of subjects with serious adverse reactions; • Proportion of subjects who prematurely discontinued neoadjuvant therapy due to adverse reactions | up to 65 weeks | 
| immunogenicity assessment | Proportion of subjects with binding and neutralizing antibodies | pre-dose to week 52, 5 timepoints | 
| Pharmacokinetics assessment | Cmin - minimum observed product concentration ; Ceoi - concentration at the end of each infusion | pre-dose to week 18, 12 timepoints |