NOV120101 Phase 2 Study in NSCLC Patients With Aquired Resistance to 1st Generation EGFR Tyrosine Kinase Inhibitors

Study Overview
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Brief Summary
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The purpose of this open-label, single-arm, multi-center phase II trial is to evaluate the efficacy and safety of novel pan-HER inhibitor, NOV120101 (Poziotinib), as a 2nd line monotherapy agent in lung adenocarcinoma patients with acquired resistance to prior EGFR tyrosine kinase inhibitors (TKIs).

Detailed Description
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Acquired resistance to prior EGFR TKIs is considered as unmet medical need in clinical practice. To evaluate the efficacy of NOV120101 (Poziotinib) as a second-line monotherapeutic agent, patients with acquired resistance to gefitinib or erlotinib will be enrolled in this study. Subjects will receive NOV120101 (Poziotinib) 16 mg PO once daily until disease progression or unacceptable toxicity development. Progression free survival (PFS) will be analyzed as the primary endpoint in this trial. Secondary endpoints including PFS rate at 16 weeks, ORR and DCR will also be analyzed.

Official Title
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Phase II Exploratory Trial to Evaluate the Efficacy and Safety of NOV120101 (Poziotinib) in Lung Adenocarcinoma Patients With Acquired Resistance to 1st Generation EGFR Tyrosine Kinase Inhibitors

Conditions
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Increased Drug Resistance

Intervention / Treatment
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* Drug: NOV120101 (Poziotinib)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 20 years or older Pathologically confirmed stage IIIB (unresectable) or IV lung adenocarinoma Patients who have 1 or more than 1 measurable or evaluable but unmeasurable lesions according to RECIST ver1.1 Patients who received prior 1st generation EGFR TKIs (gefitinib or erlotinib) monotherapy and meet the following criteria: Patients with EGFR mutation (e.g., G719X, exon 19 deletion, L858R, L861Q, etc) known to be associated with sensitivity to TKIs Patients who showed objective clinical benefit from treatment with an EGFR TKI as defined by either: Patients who showed complete (CR) or partial response (PR), or Patients who maintained stable disease (SD) status ≥ 6 months Patients who showed progressive disease (PD, RECIST ver1.1) while on continuous treatment with gefitinib or erlotinib within the last 30 days (However, patients whose progressive disease is limited in the brain cannot participate in this trial.) No intervening systemic chemotherapy between cessation of the EGFR TKI and participation of this study Patients who agree to the collection of tumor tissue specimen ECOG performance status ≤ 2 Life expectancy of ≥ 12 weeks Adequate hematological, hepatic and renal functions: WBC ≥ 4,000/mm3, Platelet ≥ 100,000/mm3, Serum creatinine ≤ 1.5 X ULN, AST and ALT ≤ 2.5 X ULN, Total bilirubin ≤ 1.5 X ULN Patients who give written informed consent voluntarily Exclusion Criteria: Patients who receive IP within 3 days from prior treatment with gefitinib or erlotinib NCI-CTCAE grade > 1 adverse events due to treatment with gefitinib or erlotinib Prior systemic chemo, immuno, hormonal and/or biological therapy except gefitinib or erlotinib within 4 weeks before IP administration Acquired resistance to EGFR TKI due to conversion of adenocarcinoma into small cell lung cancer Patients who received major surgery within 4 weeks before IP administration Symptomatic CNS metastases (patients with radiologically and neurologically stable metastases and being off corticosteroids for at least 4 weeks are able to participate in this trial.) History of other malignancies except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for ≥ 3 years and considered to be cured by investigator's judgment Known pre-existing interstitial lung disease (ILD) NYHA class III or IV heart failure, uncontrolled hypertension, unstable angina or myocardial infarction within 6 months, poorly controlled arrhythmia or other clinically significant cardiovascular abnormalities at investigator's discretion Patients whose left ventricle ejection fraction (LVEF) is below the institutional lower limit of normal (if no lower limit of normal is defined in the site, the lower limit is 50%.) Patients with known active hepatitis B, HIV infection, or other uncontrolled infectious disease Clinically significant or recent acute gastrointestinal disorders with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption disorders, CTCAE grade ≥ 2 diarrhea due to any etiology) Patients who cannot receive IP by mouth and be diagnosed with clinically significant gastrointestinal disorders which can prevent administration, transit or absorption of the IP Pregnancy or breast-feeding Women of childbearing potential (WOCBP) or men who are unwilling to use adequate contraception or be abstinent during the trial and for at least 2 months after the end of treatment Patients who received other investigational products except gefitinib and erlotinib within 4 weeks before participation Patients who cannot participate in this trial by investigator's judgment

Ages Eligible for Study
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Minimum Age: 20 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: NOV120101 (Poziotinib)<br>16 mg PO once daily until disease progression or unacceptable toxicity development | Drug: NOV120101 (Poziotinib)<br>* 16 mg PO once daily until disease progression or unacceptable toxicity development<br>* Other names: HM781-36B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | The length of time during and after medication or treatment during which the disease being treated (usually cancer) does not get worse. | By 1 year after enrollment of the last subject | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS rate at 16 weeks | The proportion of Patients maintaining progress-free status at 16 weeks | 16 weeks | 
| Objective response rate (ORR) | The proportion of patients with partial response or complete response at their best tumor treatment evaluation | By 1 year after enrollment of the last subject | 
| Disease control rate (DCR) | The proportion of patients with CR, PR and/or stable disease (SD) | By 1 year after enrollment of the last subject | 
| Overall survival (OS) |  | By 1 year after enrollment of the last subject | 
| Time to progression (TTP) |  | By 1 year after enrollment of the last subject | 
| Time to objective response |  | By 1 year after enrollment of the last subject | 
| Duration of objective response |  | By 1 year after enrollment of the last subject | 
| Duration of disease control |  | By 1 year after enrollment of the last subject | 
| Change of quality of life (QoL) measured by EQ-5D questionnaire |  | baseline and the end of treatment, by 1 year after enrollment of the last subject | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EGFR Tyrosine Kinase Inhibitor, Aquired resistance to EGFR TKI, Pan-Her inhibitor