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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Inetetamab; Drug: Pyrotinib; Drug: Oral Vinorelbine Tartrate

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 Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiang Huang; Phone Number: +8613701473675; Email: lorelai@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • The First Affiliated Hospital with Nanjing Medical University
      • Contact: Xiang Huang; Phone Number: +8613701473675; Email: lorelai@njmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Inetetamab combined with Pyrotinib plus Oral Vinorelbine; 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; Patients with HER2-positive metastatic breast cancer after progression on trastuzumab are enrolled and receive treatment.; Drug: Pyrotinib; Patients with HER2-positive metastatic breast cancer after progression on trastuzumab are enrolled and receive treatment.; Drug: Oral Vinorelbine Tartrate; Patients with HER2-positive metastatic breast cancer after progression on trastuzumab are enrolled and receive treatment.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploration of biomarkers	To explore the potential biomarkers for the efficacy of combined therapy. The biomarkers will be tested by next-generation sequence	1 year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: Xiang Huang, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2022
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 23, 2023
• First Submitted That Met QC Criteria: April 10, 2023
• First Posted (Actual): April 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Vinorelbine
• Other Study ID Numbers: 2022-SR-494

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No