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

Phase 2

Recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Inetetamab; Drug: Pyrotinib; Drug: Oral Vinorelbine Tartrate

• Registration Number: NCT05823623
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

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.

Study Timeline

• Study Start: 2022-02-13
• Study First Submitted: 2023-03-23
• Study First Submitted QC: 2023-04-10
• Study First Posted: 2023-04-21
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-13
• Last Update Posted: 2023-09-14
• Primary Completion: 2023-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Inetetamab combined with Pyrotinib plus Oral Vinorelbine	Oral Vinorelbine Tartrate	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.
Inetetamab combined with Pyrotinib plus Oral Vinorelbine	Inetetamab	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.
Inetetamab combined with Pyrotinib plus Oral Vinorelbine	Pyrotinib	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.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival，PFS	2 years	The time from the beginning of treatment to the progression or death of the patient

Secondary Outcome Measures

Name	Time	Method
overall survival，OS	4 years	The time from the beginning of treatment to the death of the patient
Objective Response Rate，ORR	2 year	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)
Clinical Benefit Rate，CBR	2 year	the percentage of participants whose best overall response, is either CR, PR or stable disease (SD) lasting for at least 24 weeks
adverse events	2 years	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.

Trial Locations

Locations (1)

The First Affiliated Hospital with Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China