A Study of MRG002 in the Treatment of Patients With HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer

The primary objective of Phase II is to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of MRG002 in patients with HER2-positive, unresectable locally advanced or metastatic breast cancer. The primary objective of Phase III is to evaluate the efficacy and safety of MRG002 versus Trastuzumab Emtansine (T-DM1) in patients with HER2-positive unresectable locally advanced or metastatic breast cancer who have been previously treated with trastuzumab (or a biosimilar) and an anti-HER2 tyrosine kinase inhibitor (anti-HER2-TKI) and have progressed on or after the most recent therapy.

Study Overview

• Status: Recruiting
• Conditions: Advanced Breast Cancer; Metastatic Breast Cancer
• Intervention / Treatment: Drug: MRG002; Drug: Trastuzumab Emtansine for Injection

• Study Type: Interventional
• Enrollment (Anticipated): 350
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Active, not recruiting
      • Anhui Provincial Hospital
  • Beijing
    • Beijing, Beijing, China, 100730
      • Not yet recruiting
      • Peking Union Medical College Hospital
      • Contact: Hongyan Ying; Phone Number: (86-10)-69156699; Email: yinghy15@163.com
    • Beijing, Beijing, China, 100071
      • Recruiting
      • Fifth Medical Center of Pla General Hospital
      • Contact: Zefei Jiang, Doctor; Phone Number: 13901372170; Email: jiangzefei@csco.cog.cn
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Active, not recruiting
      • Chongqing Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Active, not recruiting
      • Guangdong Provincial People's Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 050035
      • Not yet recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Yunjiang Liu, Doctor; Phone Number: 13703297890; Email: lyj818326@126.com
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Active, not recruiting
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China, 450052
      • Not yet recruiting
      • The First Affiliated Hosipital Of Zhengzhou University
      • Contact: Yuanting Gu; Phone Number: 0371-66913114; Email: guyuanting2009@163.com
  • Hunan
    • Changsha, Hunan, China, 410013
      • Active, not recruiting
      • Hunan Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Active, not recruiting
      • Jiangsu Province Hospital
    • Xuzhou, Jiangsu, China, 221009
      • Active, not recruiting
      • Xuzhou Central Hospital
  • Jilin
    • Changchun, Jilin, China, 130012
      • Active, not recruiting
      • Jilin Cancer Hospital
  • Liaoning
    • Shengyang, Liaoning, China, 110801
      • Active, not recruiting
      • Liaoning Cancer Hospital & Institute
  • Shandong
    • Jinan, Shandong, China, 250013
      • Active, not recruiting
      • Jinan Central Hospital Affiliated to Shandong University
  • Shanghai
    • Shanghai, Shanghai, China, 200120
      • Not yet recruiting
      • Shanghai East Hospital
      • Contact: Qun Li; Phone Number: 021-38804518; Email: liqun@fudan.edu.cn
  • Tianjing
    • Tianjing, Tianjing, China, 300060
      • Active, not recruiting
      • Tianjin Medical University Cancer Institute & Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Active, not recruiting
      • The Second Affiliated Hospital Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310005
      • Active, not recruiting
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310020
      • Not yet recruiting
      • Sir Run Run Shaw Hospital
      • Contact: Xian Wang; Phone Number: 0571-8609 0073; Email: wangxian@srrsh.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Aged 18 to 75 (including 18 and 75)，both genders;

  2. Expected survival time ≥ 6 months;

  3. The score of ECOG for performance status is 0 or 1;

  4. Patients with histologically and/or cytologically confirmed HER2-positive invasive breast cancer, including unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (MBC);

  5. Phase II: patients with advanced or metastatic disease who have previously failed trastuzumab (containing trastuzumab biosimilar) ± pertuzumab and taxane, or progressed within 12 months after neoadjuvant or adjuvant therapy (using trastuzumab (containing trastuzumab biosimilar) ± pertuzumab and taxane regimen); patients who have failed TKI and/or HER2-targeted ADCs can also be included. Phase III: patients who have received 1 or 2 prior lines of anti-HER2 therapy for locally advanced or recurrent/metastatic breast cancer (in the case of (neo) adjuvant therapy, such (neo) adjuvant therapy also counts as one line of anti-HER2 therapy if relapse occurs within 12 months of (neo) adjuvant therapy); have received prior treatment with trastuzumab (containing a trastuzumab biosimilar) and anti-HER2-TKI; have not received prior treatment with ADCs;

  6. Patients must have imaging evidence of tumor progression during or after the most recent treatment confirmed by the investigator and have at least one measurable lesion baseline according to RECIST 1.1;

  7. Organ functions must meet the basic requirements;

  8. Reproductive male and female patients of childbearing age shall be willing to take effective contraceptive measures from the date of signing the ICF to 6 months after the last dose. Women of childbearing potential must have a negative pregnancy test within 7 days before the first dose.

Exclusion Criteria:

• 1. History of other primary malignancies;

  2. Received investigational drugs from other clinical trials, any anti-tumor drugs, or radiotherapy within 4 weeks prior to the first dose/randomization; or use of endocrine therapy for breast cancer within 7 days prior to the first dose/randomization, or have current requirement of endocrine therapy; or have received strong CYP3A4 inhibitors or inducers within 2 weeks prior to the first dose/randomization, or have current requirement of CYP3A4 inhibitors or inducers; cumulative doxorubicin up to 450 mg/m2 or equivalent prior to the first dose/randomization; or had major surgery within 4 weeks prior to the first dose/randomization without full recovery or planned surgery within 12 weeks after study treatment;

  3. Presence of central nervous system (CNS) metastasis;

  4. The pleural or peritoneal effusion with combined clinical symptoms, which seriously endangers the life safety of the subjects or urgently needs clinical treatment. Or the pericardial effusion with combined clinical symptoms;

  5. Any severe or uncontrolled systemic disease, uncontrolled heart disease, uncontrolled diabetes, and active bleeding signs judged by the investigator;

  6. Evidence of active infection, including hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection, active bacteria infection requiring systematic anti-infective therapy, infection caused by other viruses, fungi, rickettsia or parasites;

  7. History of hypersensitivity to any component of MRG002 or history of hypersensitivity of ≥ Grade 3 to trastuzumab injection;

  8. Subjects with active autoimmune disease or a history of autoimmune disease are receiving immunosuppressive agents or systemic hormone therapy, and are still receiving within 2 weeks prior to enrollment/randomization;

  9. History of interstitial pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc;

  10. Other conditions inappropriate for participation in this study, as deemed by the investigator;

  11. Presence of peripheral neuropathy > Grade 1;

  12. History of cirrhosis (decompensated cirrhosis Child-Pugh class B, C).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MRG002; MRG002 will be administrated via intravenous infusion of 2.6 mg/kg once on Day 1 of every 3 weeks (21-day cycle).	Drug: MRG002; Administrated intravenously
Active Comparator: Trastuzumab Emtansine for Injection; Trastuzumab Emtansine for Injection will be administrated via intravenous infusion of 3.6 mg/kg once on Day 1 of every 3 weeks (21-day cycle).	Drug: Trastuzumab Emtansine for Injection; Administrated intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by Independent Review Committee (IRC)	PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause assessed by Independent Review Committee (IRC) according to RECIST v1.1.	Baseline to study completion（up to 36 months）

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	The proportion of patients with positive ADA immunogenicity results.	Baseline to 30 days after the last dose of study treatment
Adverse Events (AEs)	Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug.	Baseline to 30 days after the last dose of study treatment
Objective Response Rate (ORR)	ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) according to RECIST v1.1.	Baseline to study completion (up to 36 months)
Duration of Response (DoR)	DoR is defined as the time from first documented objective response (CR/PR) to the first onset of tumor progression or death of any nonsurgical cause.	Baseline to study completion (up to 36 months)
Overall Survival (OS)	OS is defined as the duration from the start of treatment to death of any cause.	Baseline to study completion (up to 36 months)
Disease Control Rate (DCR)	DCR is defined as the proportion of subjects achieving CR, PR, and stable disease (SD) after treatment.	Baseline to study completion (up to 36 months)
PFS by investigator	PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause.	Baseline to study completion (up to 36 months)
Concentration-time curve	Plot of drug concentration changing with time after drug administration.	Baseline to 30 days after the last dose of study treatment

Collaborators and Investigators

• Sponsor: Shanghai Miracogen Inc.
• Investigators: Principal Investigator: Zefei Jiang, Doctor, Fifth Medical Center of Pla General Hospital; Principal Investigator: Yunjinang Liu, Doctor, The Fourth Hospital of Hebei Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 14, 2021

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 16, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: HER2; MRG002; Antibody Drug Conjugate (ADC); Breast Cancer (BC)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine
• Other Study ID Numbers: MRG002-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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