Phase II Clinical Study of Pyrotinib in First-line Treatment of Primary HER2-amplified/Mutated Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a multicenter, single-arm phase II clinical study to evaluate the safety and efficacy of pyrotinib maleate as a first-line treatment for HER2-mutated or amplified non-small cell lung cancer. Pyrotinib maleate is a small molecule tyrosine kinase inhibitor that can irreversibly inhibit HER1, HER2, and HER4.

Official Title
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Phase II Clinical Study of Pyrotinib in First-line Treatment of Primary HER2-amplified/Mutated Advanced Non-small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pyrotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age: ≥18 years old; 2. Histologically confirmed stage IIIB or IV non-small cell lung cancer; 3. Have not previously received systemic anticancer therapy for stage IIIB or IV NSCLC; 4. HER2 insertion mutation, primary HER2 point mutation or primary HER2 amplification confirmed by genetic testing of tumor tissue or blood, pleural effusion, cerebrospinal fluid and other specimens; 5. There is at least one measurable lesion determined based on RECIST 1.1; 6. ECOG score 0-1 points; 7. Expected survival period ≥ 12 weeks; 8. Cardiac ultrasound examination showed that left ventricular ejection fraction (LVEF) ≥ 50%; 9. The patient's bone marrow function, liver and kidney function were confirmed to meet the following requirements by laboratory tests before the first administration: Neutrophil count (ANC) ≥ 1,500/mm3 (1.5×109/L); Platelet count (PLT) ≥ 75,000/mm3 (75×109/L); Hemoglobin (Hb) ≥ 8 g/dL (80 g/L); Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 60 mL/min; Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 2.5 times the upper limit of normal (ULN), patients with liver metastases should be ≤ 5×ULN. 10. The subjects voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with the follow-up. Exclusion Criteria: 1. Previous use of EGFR TKI therapy; 2. Participated in clinical trials of other drugs within 4 weeks before the start of the study; 3. Symptomatic brain metastases or meningeal metastases; 4. Insufficient bone marrow reserve or insufficient organ function; 5. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow drugs, etc., may affect the intake, transport or absorption of drugs; 6. Received major surgical operation or severe traumatic injury, fracture, or poor healing wound within 4 weeks; 7. Known history of other malignancies, unless the subject has received potentially curative therapy prior to initiation of therapy and has at least 3 years of evidence of disease-free recurrence (non-small cell lung cancer, radical skin basal cell undergoing successful resection) carcinoma, superficial bladder cancer, squamous cell carcinoma of the skin, cervical carcinoma in situ or other carcinoma in situ); 8. Those who have serious adverse reactions and allergies to the drugs and excipients used in this group; 9. Pregnant or lactating female patients, female patients with fertility and positive baseline pregnancy test, or patients of childbearing age who are unwilling to take effective contraceptive measures throughout the trial; 10. The patient has serious concomitant diseases, or any other condition that the investigator considers the patient unsuitable to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: pyrotinib<br> | Drug: Pyrotinib<br>* Pyrotinib maleate is a small molecule tyrosine kinase inhibitor that can irreversibly inhibit HER1, HER2, and HER4.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | It is defined as the proportion of patients whose tumors shrink to a predetermined size and maintain a minimum time limit. It includes the cases of CR and PR. | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | From the date Into this study to tumor progression or death for any | 1 year | 
| DCR | the rate of CR, PR plus SD | 2 year | 
| AEs and SAEs | Number of Participants With adverse events (AEs) and serious adverse events (SAEs) Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. | 1 year | 
| QoL | The quality of life of the subjects was assessed according to the EORTC QLQ-C30 quality of life questionnaire. | 1 year |