Clinical trial NCT04941885: Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus Aromatase Inhibitor in Metastatic HER2+/HR+ Breast Cancer
Official title: A Phase II Single-arm Clinical Trial of the Efficacy and Tolerability of Inetetamab Combined With Cyclophosphamide Metronomic Chemotherapy and Aromatase Inhibitor in Metastatic HER2+/HR+ Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2021-06-28
Enrollment: 78
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 1 year
Secondary outcomes:
measure: Clinical benefit rate (CBR)
timeFrame: 1 year
measure: Progression free survival (PFS)
timeFrame: 1 year
measure: Duration of response (DOR)
timeFrame: 1 year
measure: Overall survival (OS)
timeFrame: 3 years
measure: Number of Participants with Adverse Events
timeFrame: 1 year
measure: The quality of life
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Shusen Wang
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Shusen Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: