Inetetamab Combined With Pyrotinib Plus Oral Vinorelbine for the Treatment of HER2-positive Metastatic Breast Cancer

Study Overview
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Brief Summary
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In this phase 2 single-arm clinical trial, 30 patients with HER2-positive metastatic breast cancer after progression on trastuzumab are enrolled and receive treatment of Inetetamab plus Pyrotinib plus Oral Vinorelbine. The study aimed to access the efficacy and safety of Inetetamab combined with Pyrotinib and Oral Vinorelbine in HER2-positive metastatic breast cancer patients after progression on trastuzumab.

Detailed Description
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Trastuzumab is an important agent for the treatment of patients with HER2-positive metastatic breast cancer. However, a considerable number of patients will develop resistance to trastuzumab treatment. Previous studies have shown that multiple mechanisms mediate trastuzumab resistance, such as abnormal extracellular domain of the HER2 receptor, HER3 mutation and activation of bypass signaling pathway. To overcome these resistance mechanisms, the combination of trastuzumab with HER2-targeting tyrosine kinase inhibitor (TKI) is an effective strategy. In this phase 2 single-arm clinical trial, 30 patients with HER2-positive metastatic breast cancer after progression on trastuzumab are enrolled and receive treatment of Inetetamab plus Pyrotinib plus Oral Vinorelbine. The study aimed to access the efficacy and safety of Inetetamab combined with Pyrotinib and Oral Vinorelbine in HER2-positive metastatic breast cancer patients after progression on trastuzumab. The primary end point is Progressive-free Survival (PFS). The secondary end points are Overall Survival (OS), Overall Response Rate (ORR), Clinical Benefit Rate (CBR) and safety.

Official Title
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A Phase II Single-arm Clinical Trial of Inetetamab Combined With Pyrotinib Plus Oral Vinorelbine for the Treatment of Patients With HER2-positive Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Inetetamab
* Drug: Pyrotinib
* Drug: Oral Vinorelbine Tartrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, Aged ≥ 18 years. Metastatic breast cancer confirmed by pathology or imaging. Pathological diagnosis of HER2 positive (definition: immunohistochemical (IHC) 3+, or IHC 2+ with in situ hybridization (ISH) testing of amplification. Previously received trastuzumab treatment. At least one Measurable target lesion according to RECIST 1.1. Eastern Cooperative Oncology Group (ECOG) score 0- 2. Sufficient organ function: Neutrophil count (ANC) ≥ 1.5 × 10 ^ 9 / L, Platelet count (PLT) ≥ 100 × 10 ^ 9 / L, hemoglobin (Hb) ≥90 g/L，total bilirubin (TBIL) ≤ 1.5 × upper limit of normal value (ULN), alanine aminotransferase (ALT / AST) ≤ 2.5 × ULN (liver metastasis patients ≤ 5×ULN), serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCR) ≥ 60 ml/min, Left ventricular ejection fraction (LVEF) ≥50%. Exclusion Criteria: Allergic to the ingredients of the study drug. Symptomatic brain or meningeal metastasis. Gastrointestinal dysfunction or gastrointestinal diseases (including active ulcers). LVEF <50%; clinical manifestations of patients with obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency, and severe valvular disease. Any other medical, social or psychological conditions which are inappropriate to participate in this trial. Pregnant or lactating women, women of childbearing age who refused to take effective contraceptive measures during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inetetamab combined with Pyrotinib plus Oral Vinorelbine<br>Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, intravenous, every 3 weeks for one cycle. Pyrotinib: 400mg, oral, every day. Vinorelbine: 60mg/m2, oral, every week. | Drug: Inetetamab<br>* Patients with HER2-positive metastatic breast cancer after progression on trastuzumab are enrolled and receive treatment.<br>Drug: Pyrotinib<br>* Patients with HER2-positive metastatic breast cancer after progression on trastuzumab are enrolled and receive treatment.<br>Drug: Oral Vinorelbine Tartrate<br>* Patients with HER2-positive metastatic breast cancer after progression on trastuzumab are enrolled and receive treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival，PFS | The time from the beginning of treatment to the progression or death of the patient | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival，OS | The time from the beginning of treatment to the death of the patient | 4 years | 
| Objective Response Rate，ORR | The percentage of participants whose best overall response, according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, is either complete response (CR) or partial response (PR) | 2 year | 
| Clinical Benefit Rate，CBR | the percentage of participants whose best overall response, is either CR, PR or stable disease (SD) lasting for at least 24 weeks | 2 year | 
| adverse events | The probability and severity of adverse reactions related to the treatment were assessed by CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) v5.0. | 2 years |