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

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04924699
• Other study ID #: MRG002-004
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 30, 2021
• Est. completion date: October 2023

Study information

• Verified date: March 2023
• Source: Shanghai Miracogen Inc.
• Contact: Program Director
• Phone: 86-21-61637960
• Email: clinicaltrials[@]miracogen.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: October 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• MRG002
Administrated intravenously
• Trastuzumab Emtansine for Injection
Administrated intravenously

Locations

Country	Name	City	State
China	Fifth Medical Center of PLA General Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital	Hangzhou	Zhejiang
China	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	Jinan Central Hospital Affiliated to Shandong University	Jinan	Shandong
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Shanghai East Hospital	Shanghai	Shanghai
China	Liaoning Cancer Hospital & Institute	Shengyang	Liaoning
China	The Fourth hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Tianjin Medical University Cancer Institute & Hospital	Tianjing	Tianjing
China	Xuzhou Central Hospital	Xuzhou	Jiangsu
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hosipital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Miracogen Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	Concentration-time curve	Plot of drug concentration changing with time after drug administration.	Baseline to 30 days after the last dose of study treatment
Secondary	Immunogenicity	The proportion of patients with positive ADA immunogenicity results.	Baseline to 30 days after the last dose of study treatment