Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus Aromatase Inhibitor in Metastatic HER2+/HR+ Breast Cancer

NCT ID: NCT04941885

Last Updated: 2021-07-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-25
• Study Completion Date: 2025-07-01

Brief Summary

Antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the important mechanisms for suppressing tumors of Trastuzumab. Pre-clinical data suggest that the ADCC effect of Inetetamab, an anti-HER2 monoclonal antibody with a modified Fc segment, is 1.11 times that of trastuzumab. Previous studies indicated that enhanced ADCC effects can be transformed into clinical benefits. Immune induction through cyclophosphamide metronomic chemotherapy may further enhance the ADCC effect of anti-HER2 monoclonal antibodies. Therefore, we conducted this study to explore the efficacy and the safety of Inetetamab combined with cyclophosphamide metronomic chemotherapy and aromatase inhibitors(AI) in the treatment of metastatic HER2-positive and HR-positive breast cancer patients and to explore the possible mechanisms.

Detailed Description

Trastuzumab is a humanized monoclonal antibody, and antibody-dependent cell-mediated cytotoxicity (ADCC) is one of its important mechanisms for suppressing tumors. Pre-clinical data suggest that the ADCC effect of Inetetamab, an anti-HER2 monoclonal antibody with a modified Fc segment, is 1.11 times that of trastuzumab. Previous studies indicated that enhanced ADCC effects can be transformed into clinical benefits, but the absolute benefits are still unsatisfactory. Further improvement of ADCC effects and monoclonal antibody-induced immune responses may improve the clinical benefits. Immune induction through cyclophosphamide metronomic chemotherapy may further enhance the ADCC effect of anti-HER2 monoclonal antibodies. According to previous clinical studies, for HR-positive and HER2-positive metastatic breast cancer patients, metronomic chemotherapy combined with endocrine therapy and anti-HER2 targeted therapy may be one of the treatment options. Therefore, we conducted this study to explore the efficacy and the safety of Inetetamab combined with cyclophosphamide metronomic chemotherapy and aromatase inhibitors(AI) in the treatment of metastatic HER2-positive and HR-positive breast cancer patients, and we further exploring the possible mechanisms.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus AI

Each participant receives Inetetamab(8mg/kg iv day 1 followed by 6mg/kg iv day 1, cycled every 21 days) plus cyclophosphamide metronomic chemotherapy(50mg once a day orally) plus aromatase(once a day orally).

Group Type: EXPERIMENTAL

Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus AI

Intervention Type: DRUG

Each participant receives Inetetamab plus cyclophosphamide metronomic chemotherapy plus AI.

Interventions

Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus AI

Each participant receives Inetetamab plus cyclophosphamide metronomic chemotherapy plus AI.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Voluntarily sign the informed consent form;

2. 18-75 years old;

3. The expected survival period is ≥12 weeks;

4. Eastern Cooperative Oncology Group (ECOG) score [0-2] points;

5. The diagnosis of invasive carcinoma by histology or cytology; Estrogen receptor (ER) positive (defined as >1% nuclear ER staining); HER2 negative (defined as IHC 0 or 1+, or HER2(2+) with HER2 FISH detection no amplification);

6. Inoperable or recurrent/metastatic breast cancer patients with aromatase inhibitor treatment failure;

7. In the state of disease progression before enrollment;

8. Measurable disease according to RECIST version 1.1 or only bone metastasis;

9. Adequate hematological, hepatic and renal function;

10. NYHA class I or II and Left ventricular ejection fraction (LVEF) ≥50%.

11. The diagnosis of invasive carcinoma by histology or cytology: Hormone receptor (HR) positive (defined as >1% nuclear estrogen receptor staining); HER2 positive (defined as IHC 3+, or HER2 FISH detection amplification);

12. In the state of disease progression before enrollment;

13. Have lesions able to and agree to perform tissue biopsy at the time requested in the study;

14. Treatment ≥1 line after recurrence/metastasis, or relapse within 12 months after completing trastuzumab-based adjuvant therapy or during trastuzumab adjuvant therapy;

15. Previously received trastuzumab for anti-HER2 therapy;

16. Measurable disease according to RECIST version 1.1.

Exclusion Criteria

1. Allergic to the ingredients of Inetetamab, cyclophosphamide or similar drugs;

2. Concomitant diseases/conditions that is not controllable, and any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the patient's participation in this study;

3. Patients who cannot accept drugs orally;

4. Women who are pregnant or breastfeeding or planning to give birth;

5. Patients with currently symptomatic brain or meningeal metastasis;

6. History of other primary malignancy;

7. Resistant to steroidal or nonsteroidal aromatase Inhibitor;

8. Have used Inetetamab;

9. Patients with life-threatening, symptomatic, metastatic visceral disease.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

wang shusen

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shusen Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Shusen Wang

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Shusen Wang, MD

Role: CONTACT

wangshs@sysucc.org.cn

+86-13926168469

Kuikui Jiang, MD

Role: CONTACT

jiangkk@sysucc.org.cn

+86-15210589011

Facility Contacts

Shusen Wang, MD

Role: primary

wangshs@sysucc.org.cn

+86-13926168469

Other Identifiers

SYSU-2021

Identifier Type: -

Identifier Source: org_study_id