Efficacy and Safety Study of EG12014 Compared With Herceptin in Subjects With HER2 Positive Early Breast Cancer

A Phase III, Randomized, Multicenter, Double-blind Study to Compare Efficacy and Safety of EG12014 With Herceptin as Neoadjuvant Treatment in Combination With Anthracycline/Paclitaxel Systemic Therapy in HER2-Positive Early Breast Cancer

The purpose of this research study is to compare the efficacy and safety of EG12014 with Herceptin as neoadjuvant treatment for 12 weeks, followed by surgery and subsequent EG12014 or Herceptin adjuvant treatment for up to 12 months.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: EG12014; Drug: Herceptin

• Study Type: Interventional
• Enrollment (Actual): 807
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Brest, Belarus
    • Brest Regional Oncology Center
  • Gomel, Belarus
    • Gomel Regional Clinical Oncology Center
  • Lesnoy, Belarus
    • N.N. Aleksandrov Republican Research Oncology and Medical Radiology Center
  • Minsk, Belarus
    • Minsk City Clinical Oncology Center
  • Mogilev, Belarus
    • Mogilev Regional Oncology Center
  • Vitebsk, Belarus
    • Vitebsk Regional Clinical Oncology Center
• Chile
  • Temuco, Chile
    • Medical Research Limited Society
  • Viña Del Mar, Chile
    • Oncocentro Apys
• Colombia
  • Medellín, Colombia
    • Clinic Life Foundation
  • Medellín, Colombia
    • Rodrigo Botero SAS
• Georgia
  • Batumi, Georgia
    • LTD High-Tech Hospital MedCenter
  • Kutaisi, Georgia
    • JSC "Evex Hospitals
  • Tbilisi, Georgia
    • LTD Aversi Clinic
  • Tbilisi, Georgia
    • LTD Cancer Research Centre
  • Tbilisi, Georgia
    • LTD Acad. F. Todua Medical Center - LTD Research Institute of Clinical Medicine
  • Tbilisi, Georgia
    • LTD Health House
  • Tbilisi, Georgia
    • LTD Institute of Clinical Oncology
  • Tbilisi, Georgia
    • LTD S.Khechinashvili University Hospital
  • Tbilisi, Georgia
    • Malkhaz Katsiashvili Multiprofile Emergency Medicine Center
• India
  • Bengaluru, India
    • Cytecare Cancer Hospitals
  • Lucknow, India
    • King George's Medical University, Department of Endocrine surgery, Shatabdi Phase II
  • Mumbai, India
    • Tata Memorial Centre
  • Nagpur, India
    • HCG NCHRI Cancer Centre
  • Vellore, India
    • Christian Medical College, Department of Medical Oncology
• Korea, Republic of
  • Daegu, Korea, Republic of
    • Keimyung University - Dongsan Medical Center
• Russian Federation
  • Arkhangel'sk, Russian Federation
    • Arkhangelsk Clinical Oncology Center
  • Chelyabinsk, Russian Federation
    • Chelyabinsk Regional Clinical Oncology and Nuclear Medicine Center
  • Chelyabinsk, Russian Federation
    • Evimed, LLC
  • Ivanovo, Russian Federation
    • Ivanovo Regional Oncology Center
  • Kazan, Russian Federation
    • Republican Clinical Oncology Center
  • Krasnoyarsk, Russian Federation
    • Krasnoyarsk A.I. Kryzhanovsky Regional Oncology Center
  • Kursk, Russian Federation
    • Kursk Regional Clinical Oncology Center
  • Moscow, Russian Federation
    • N.N. Blokhin National Medical Oncology Research Center
  • Moscow, Russian Federation
    • National Medical Research Center for Radiology
  • Moscow, Russian Federation
    • Vitamed" LLC
  • Obninsk, Russian Federation
    • A.F.Tsyb Medical Radiology Research Center
  • Omsk, Russian Federation
    • Clinical Oncology Center
  • Pyatigorsk, Russian Federation
    • Pyatigorsk Interdistrict Oncology Center
  • Rostov-on-Don, Russian Federation
    • Rostov Oncology Research Institute
  • Ryazan', Russian Federation
    • Regional Clinical Oncology Center
  • Saint Petersburg, Russian Federation
    • Oncology Center of Moskovskiy District
  • Saint Petersburg, Russian Federation
    • AV Medical Group
  • Saint Petersburg, Russian Federation
    • City Clinical Oncology Center
  • Saint Petersburg, Russian Federation
    • Clinic "Mart"
  • Saint Petersburg, Russian Federation
    • I.I. Mechnikov North-Western State Medical University
  • Saint Petersburg, Russian Federation
    • Leningrad Regional Oncology Center (Outpatient Department)
  • Saint Petersburg, Russian Federation
    • Leningrad Regional Oncology Center (Surgery Department)
  • Saint Petersburg, Russian Federation
    • N.N. Petrov National Medical Research Center of Oncology
  • Saint Petersburg, Russian Federation
    • Private Medical Institution "EVROMEDSERVIS", Department of Oncology
  • Saint Petersburg, Russian Federation
    • St. Petersburg Clinical Research and Practical Center for Specialized Types of Medical Care (Oncology)
  • Saransk, Russian Federation
    • Republican Oncology Center
  • Sochi, Russian Federation
    • Oncology Center #2
  • Tomsk, Russian Federation
    • Tomsk National Research Medical Center
  • Veliky Novgorod, Russian Federation
    • Regional Clinical Oncology Center
  • Volgograd, Russian Federation
    • Volgograd Regional Clinical Oncology Center
• South Africa
  • Cape Town, South Africa
    • GVI Oncology, Cape Gate Oncology Centre
  • Durban, South Africa
    • The Oncology Centre
  • Johannesburg, South Africa
    • Medical Oncology Centre of Rosebank
  • Pretoria, South Africa
    • Little Company of Mary Medical Center, Department of Oncology
  • Pretoria, South Africa
    • University of Pretoria, Department of Medical Oncology
• Taiwan
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan
    • Linkou Chang Gung Memorial Hospital
• Ukraine
  • Chernihiv, Ukraine
    • Chernihiv Regional Oncology Center
  • Chernivtsi, Ukraine
    • Chernivtsi Regional Clinical Oncology Center
  • Dnipro, Ukraine
    • Clinical Oncology Center
  • Dnipro, Ukraine
    • Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy
  • Ivano-Frankivsk, Ukraine
    • Prikarpattia Clinical Oncology Center
  • Kharkiv, Ukraine
    • Communal Non-Profit Enterprise "Regional Center of Oncology"
  • Kharkiv, Ukraine
    • State Institution: S.P. Hryhoriev Institute of Medical Radiology under the Ukrainian Academy of Medical Sciences, Department of Clinical Oncology and Hematology
  • Khmelnytskyi, Ukraine
    • Khmelnytskyi Regional Oncology Center
  • Kryvyi Rih, Ukraine
    • Kryvyi Rih Oncology Center, Department of Chemotherapy
  • Kyiv, Ukraine
    • Medical Center of First Private Clinic
  • Kyiv, Ukraine
    • Kyiv City clinical Hospital #2
  • Kyiv, Ukraine
    • Kyiv Regional Oncology Center, Department of Mastology
  • Kyiv, Ukraine
    • Medical Center "Verum"
  • Luts'k, Ukraine
    • Volyn Regional Oncology Center, Department of Chemotherapy
  • Lviv, Ukraine
    • Public Institution under Lviv Regional Council: Lviv Regional Treatment and Diagnostics Oncology Center, Department of Chemotherapy
  • Mariupol, Ukraine
    • Mariupol Oncology Center
  • Odesa, Ukraine
    • Odesa Regional Oncology Center
  • Odesa, Ukraine
    • Odesa Regional Clinical Hospital, Center for Mastology, Department of Thoracic Surgery
  • Ternopil', Ukraine
    • Ternopil Regional Clinical Oncology Center, Department of Chemotherapy
  • Uzhhorod, Ukraine
    • Central City Clinical Hospital, Department of Oncology and Radiology
  • Uzhhorod, Ukraine
    • Zakarpattia Regional Clinical Oncology Center, Department of Chemotherapy
  • Vinnytsia, Ukraine
    • Podillia Regional Oncology Center
  • Zhytomyr, Ukraine
    • Zhytomyr Regional Oncology Center
• United States
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Detroit Clinical Research Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Aultman Hospital, Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

1. Provide signed and dated written informed consent before entering the study. The informed consent will cover both parts of the study (neoadjuvant part and adjuvant part).
2. Female, ≥18 and ≤65 years of age.
3. Histologically-confirmed invasive carcinoma of the breast (American Joint Committee on Cancer [AJCC, vs. 8.0] Stage II, IIIa).
4. Operable breast cancer, planned surgical resection of breast tumor (mastectomy or lumpectomy) and sentinel or axillary lymph nodes.
5. Unilateral, measurable tumor of the breast >2 cm in diameter.
6. HER2 positive tumor, defined as 3+ score by IHC or fluorescence positive by FISH, as confirmed by central laboratory.
7. Known estrogen receptor (ER) and progesterone receptor (PrR) status at study entry.
8. Adequate bone marrow function, defined as granulocyte count of ≥1.500/µL, and platelet count of ≥100.000/µL.

9. Adequate hepatic and renal function, defined as:

   bilirubin within normal range

   alanine aminotransferase (ALT) ≤2 x upper limit of normal (ULN)

   aspartate aminotransferase (AST) ≤2 x ULN

   gamma glutamyl transferase (GGT) ≤3 x ULN

   serum creatinine <1.5 ULN

10. International normalized ratio ≤1.5×ULN (2 to 3×ULN if on anticoagulants) or prothrombin time ≤1.5×ULN; activated partial thromboplastin time ≤1.5×ULN.
11. Hemoglobin concentrations ≥10 g/dL.
12. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
13. LVEF ≥55%, measured by multiple-gated acquisition (MUGA) scan or echocardiography.
14. Negative pregnancy test at entry, women of childbearing potential have to use contraceptives during the course of the study.

Females with childbearing potential must provide a negative serum pregnancy test at Screening and must be using adequate birth control. Adequate birth control is defined as agreement to consistently practice an effective and accepted method of contraception throughout the duration of the study and for 7 months after study drug treatment. These methods include hormonal contraceptives, intrauterine device, or double barrier contraception (i.e., condom + diaphragm) or a male partner with documented vasectomy.

Non-childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start.

Exclusion Criteria:

1. Bilateral breast cancer.
2. Pregnancy or lactation or considering becoming pregnant.
3. Metastases, other than sentinel/axillary lymph nodes.
4. Previous treatment (chemotherapy, biologic therapy, radiation, or surgery) for invasive malignant disease or other concomitant malignancy, other than basal cell carcinoma of the skin. Previous treatment for carcinoma in situ of the cervix is allowed.
5. Previous treatment with Herceptin.
6. Angina pectoris or arrhythmia requiring medication; poorly controlled hypertension; history of myocardial infarction or cardiac failure, New York Heart Association (NYHA) class II or higher; clinically significant cardiac valvular disease; hemodynamic effective pericardial effusion; other cardiomyopathies; LVEF of <55%.
7. Any investigational treatment less than 30 days prior to study entry, or within a time interval less than at least 5 half-lives of the investigational medicinal product, whichever is longer.
8. Positive diagnostic test for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
9. History of hypersensitivity to drugs with similar chemical structures to trastuzumab.
10. History of, or known current problems with, drug or alcohol abuse.
11. Other serious illness, medical disorder or condition that, in the opinion of the Investigator, would make the patient unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EG12014; Epirubicin and cyclophosphamide followed by EG12014 plus paclitaxel. All patients will be scheduled for surgery (breast and axillary lymph nodes) at 3 to 6 weeks after completion of neoadjuvant chemotherapy.	Drug: EG12014; EG12014 6mg/kg is ongoing to be administered after 8mg/kg loading dose.
Active Comparator: Herceptin; Epirubicin and cyclophosphamide followed by Herceptin plus paclitaxel. All patients will be scheduled for surgery (breast and axillary lymph nodes) at 3 to 6 weeks after completion of neoadjuvant chemotherapy.	Drug: Herceptin; Herceptin 6mg/kg is ongoing to be administered after 8mg/kg loading dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of pathologic complete response (pCR) at time of surgery	pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled sentinel and/or axillary lymph nodes	At the time of surgery (3-6 weeks after completion of neoadjuvant chemotherapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR at the time of surgery	pCR is defined as the absence of residual invasive cancer and of DICS (ypT0 ypN0) from breast tissue and sentinel/axillary lymph nodes, as assessed by central laboratory	At the time of surgery (3-6 weeks after completion of neoadjuvant chemotherapy)
pCR at the time of surgery	pCR is defined as the absence of invasive cancer in breast tissue only (ypT0/is) as assessed by central laboratory	At the time of surgery (3-6 weeks after completion of neoadjuvant chemotherapy)
Event-free survival (EFS) up to end of study (EOS)	EFS is defined as time from initial randomization to the date when disease recurrence or progression (local, regional, distant or contralateral) is diagnosed according to institutional standard, or date of death of any cause, whichever is earlier	Randomization to date of progression or end of study (up to approximately 24 months or death)
Overall response (OR) prior to surgery	Objective response is defined as partial response (PR) or complete response (CR) according to RECIST v1.1	At screening and prior to surgery (3-6 weeks after completion of neoadjuvant chemotherapy)
Overall survival (OS) up to End of Study (EOS)	OS up to EOS is defined as time from the date of initial randomization to the date of death	Randomization to end of study (up to approximately 24 months or death)
Incidence of AEs	Incidence of AEs (including severity, seriousness, and relationship to study drug) and laboratory abnormalities	From time of informed consent to end of study (up to approximately 25 months or death)
Evaluation of Immunogenicity of EG12014 and Herceptin	Titer of anti-drug antibodies (ADA)	Prior to 1st infusion of study drug, during neoadjuvant treatment, after the last dose of neoadjuvant treatment, during adjuvant treatment, and End of Treatment
Measure serum trastuzumab concentration	Measure serum trastuzumab concentration for EG12014 and Herceptin arms	Prior to 1st infusion of study drug, during neoadjuvant treatment after the last dose of neoadjuvant treatment, during adjuvant treatment, and End of Treatment

Collaborators and Investigators

• Sponsor: EirGenix, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2018
• Primary Completion (Actual): January 20, 2022
• Study Completion (Actual): January 20, 2022

Study Registration Dates

• First Submitted: February 8, 2018
• First Submitted That Met QC Criteria: February 8, 2018
• First Posted (Actual): February 14, 2018

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: January 19, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: EGC002; 2017-003973-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No