NOV120101 (Poziotinib) for 1st Line Monotherapy in Patients With Lung Adenocarcinoma

A Prospective, Open-label, Single Arm, Multi-center, Phase II Exploratory Trial to Evaluate the Efficacy and Safety of NOV120101 (Poziotinib) as the First-line Treatment Medication in Patients With Harboring EGFR Mutations

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 first-line monotherapeutic agent in patients with lung adenocarcinoma harboring EGFR mutation.

EGFR TKIs are known as more effective and less toxic medications against EGFR mutated tumors. However, newly acquired resistance to these inhibitors is the inevitable obstacle in continuous treatment with them. To overcome this problem, many new class of TKIs including NOV120101 (Poziotinib) are developing these days. To evaluate the efficacy of NOV120101 (Poziotinib) as a first-line monotherapeutic medication, chemotherapy-naïve patients will participate in this study. Subjects will receive NOV120101 (Poziotinib) 12 mg PO once daily until disease progression or unacceptable toxicity development. Objective response rate (ORR) will be analyzed as the primary endpoint in this trial. Secondary endpoints including PFS rate at 12 months, DCR, PFS, and OS will also be analyzed.

Inclusion Criteria:

1. Male or female patients aged 20 years or older
2. Pathologically confirmed stage IIIB (unresectable) or IV lung adenocarcinoma
3. Documented EGFR mutation (e.g., exon 19 deletion, exon 21 L858R, etc.) with tumor tissue
4. Patients who have 1 or more measurable lesions according to RECIST version 1.1
5. ECOG performance status 2 or less
6. Life expectancy of 12 weeks or more
7. Patients who have adequate hematological, hepatic and renal functions; WBC 4,000 or more per mm3, platelet 100,000 or more per mm3, serum creatinine 1.5 times or less upper limit of normal, AST and ALT 2.5 times or less upper limit of normal, total bilirubin 1.5 times or less upper limit of normal
8. Patients who give written informed consent voluntarily

Exclusion Criteria:

1. Prior systemic chemotherapy, immunotherapy or biological therapy for stage IIIB or IV adenocarcinoma (However, neo or adjuvant chemo, chemoradio or radiotherapy is permitted if at least 6 months has elapsed prior to disease progression)
2. Prior treatment with small molecules or antibodies targeting EGFR
3. Patients who received major surgery within 4 weeks before study drug administration
4. Symptomatic CNS metastases (patients with radiologically and neurologically stable metastases and being off corticosteroids for at least 2 weeks are able to participate in this trial.)
5. 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 or more and considered to be cured by investigator's judgment
6. Known preexisting interstitial lung disease (ILD)
7. 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
8. 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 percent)
9. Patients with known active hepatitis B, HIV infection, or other uncontrolled infectious disease
10. Clinically significant or recent acute gastrointestinal disorders with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption disorders, CTCAE grade 2 diarrhea or more due to any etiology)
11. Patients who cannot receive IP by mouth and be diagnosed with clinically significant gastrointestinal disorders which can prevent administration, transit or absorption of the study drug
12. Pregnancy or breast feeding
13. 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
14. Patients who received other investigational products except gefitinib and erlotinib within 4 weeks before participation
15. Patients who cannot participate in this trial by investigator's judgment