Clinical trial NCT05823623: Inetetamab Combined With Pyrotinib Plus Oral Vinorelbine for the Treatment of HER2-positive Metastatic Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2023-04-21
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Female, Aged ≥ 18 years.
2. Metastatic breast cancer confirmed by pathology or imaging.
3. Pathological diagnosis of HER2 positive (definition: immunohistochemical (IHC) 3+, or IHC 2+ with in situ hybridization (ISH) testing of amplification.
4. Previously received trastuzumab treatment.
5. At least one Measurable target lesion according to RECIST 1.1.
6. Eastern Cooperative Oncology Group (ECOG) score 0- 2.
7. 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:

1. Allergic to the ingredients of the study drug.
2. Symptomatic brain or meningeal metastasis.
3. Gastrointestinal dysfunction or gastrointestinal diseases (including active ulcers).
4. LVEF \<50%; clinical manifestations of patients with obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency, and severe valvular disease.
5. Any other medical, social or psychological conditions which are inappropriate to participate in this trial.
6. Pregnant or lactating women, women of childbearing age who refused to take effective contraceptive measures during the study period.

Primary outcomes:
measure: Progression Free Survival，PFS
timeFrame: 2 years
Secondary outcomes:
measure: overall survival，OS
timeFrame: 4 years
measure: Objective Response Rate，ORR
timeFrame: 2 year
measure: Clinical Benefit Rate，CBR
timeFrame: 2 year
measure: adverse events
timeFrame: 2 years
Other outcomes:
measure: Exploration of biomarkers
timeFrame: 1 year
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Xiang Huang
role: PRINCIPAL_INVESTIGATOR
References: