Phase 2 Study of Pyrotinib in Previously Treated Patients With NSCLC Having EGFR or ERBB2 Exon 20 Insertion Mutation

Study Overview
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Brief Summary
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This is a Phase 2, open-label study to evaluate the efficacy and the safety/tolerability of pyrotinib in previously treated NSCLC patients with EGFR exon 20 insertion mutations or HER2 exon 20 insertion mutations. Patient has had at least one prior systemic treatment for locally advanced or metastatic NSCLC.

Official Title
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A Phase 2 Study of Pyrotinib in Patients With Non-Small Cell Lung Cancer (NSCLC), With at Least One Prior Systemic Treatment, Locally Advanced or Metastatic, With EGFR or ERBB2 Exon 20 Insertion Mutation (PEER20)

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: 18-80years，ECOG PS：0-2，Life expectancy of more than 3 months，with measurable lesion ( RECIST1.1). Histologically or cytologic confirmed EGFR or HER2 Exon 20 Insertion Mutation positive advanced Non-small cell lung cancer who failed prior therapies. ≥1 target lesion that has not received radiotherapy in the past 3 months and can be accurately measured in at least 1 direction；Previously received radiation therapy, but the radiotherapy area must be <25% of the bone marrow area, and radiation therapy must have closed for at least≥4 weeks at the time of enrollment. Main organs function is normal. Signed and dated informed consent. Exclusion Criteria: Patient has had previous treatment with Pyrotinib, Poziotinib or any other EGFR or HER2 exon 20 insertion mutation-selective tyrosine kinase inhibitor (TKI) prior to study participation. The currently approved TKIs (ie, erlotinib, gefitinib, afatinib, osimertinib) are not considered to be exon 20 insertion-selective and are permissible Patients who planned to receive systemic anti-tumor therapy within 4 weeks prior to allocation or during the course of this study, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or receiving the Mitomycin C 6 weeks prior to medication). Extra-field radiotherapy (EF-RT) was performed 4 weeks prior to allocation or restricted radiotherapy for assessing tumor lesions within 2 weeks prior to allocation With kinds of factors which affect oral medicine (e.g. failing to swallow, gastrointestinal tract getting resected, chronic diarrhea and ileus) Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pyrotinib History of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease, or history of organ transplantation; active infection including hepatitis B (HBV DNA level ≥1000 copies /mL), hepatitis C and human immunodeficiency virus (HIV); Severe acute or chronic infections requiring systemic treatment Subjects had any heart disease, including: (1) angina; (2) requiring medication or clinically significant arrhythmia; (3) myocardial infarction; (4) heart failure; (5) Any heart diseases judged by investigator as unsuitable to participate in the trial Known history of neurological or psychiatric disease, including epilepsy or dementia Has a history of malignant tumors. Except for patients with cutaneous basal cell carcinoma, superficial bladder cancer, cutaneous squamous cell carcinoma or orthotopic cervical cancer who have undergone curative treatment and have no disease recurrence within 5 years after the start of treatment Respiratory syndrome (dyspnea≥CTC AE 2), severe pleural effusion, ascites, pericardial effusion Abnormal blood coagulation (INR>1.5 or PT > ULN + 4s or APTT > 1.5 ULN), with bleeding tendency or receiving thrombolytic or anticoagulant therapy; Renal insufficiency: urinary protein ≥ ++, or 24-hour urine protein ≥ 1.0g Patient has had other malignancies within the past 3 years, except for stable non-melanoma skin cancer, fully treated and stable early stage prostate cancer or carcinoma in situ of the cervix or breast without need of treatment Patient is pregnant or breast-feeding Judgment by the investigator that should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Previously treated patients with EGFR exon 20 insertion mutant positive NSCLC | Drug: Pyrotinib<br>* pyrotinib, single agent, 400mg p.o once daily until disease progressed<br>|
| Experimental: Cohort 2<br>Previously treated patients with HER2 exon 20 insertion mutant positive NSCLC | Drug: Pyrotinib<br>* pyrotinib, single agent, 400mg p.o once daily until disease progressed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The proportion of subjects who achieve Complete Response (CR) and Partial Response (PR) by the best response from the first dose of pyrotinib to the end of study. | To evaluate objective response rate 6-8 weeks after the initiation of pyrotinib | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | The PFS time is defined as time from enrollment to locoregional or systemic recurrence, second malignancy or death due to any cause; censored observations will be the last date of : death, last tumor assessment, last follow up date or last date in drug log | 24 months | 
| Disease Control Rate (DCR) | Disease Control Rate (DCR) defined as the percentage of participants with Disease Control best overall response (complete response, partial response or stable disease). | 24 months | 
| OS（Overall Survival） | OS was defined as time from date of enrollment to date of death due to any cause. For participants still alive at the time of analysis, OS time was censored on last date that participants were known to be alive. | 24 months | 
| Duration of Response (DoR) | Number of days from the date that measurement criteria are first met for CR or PR (whichever status is recorded first) until the first subsequent date that progressive disease or death is documented. | 24 months | 
| Safety and Tolerability | Number of Participants with treatment related Adverse Events as Assessed by CTCAE v4.0 | 24 months |