Poziotinib in Patients With HER2+ Recurrent Stage IV BC Who Have Received at Least 2 Prior HER2-directed Regimens

To evaluate the efficacy of NOV120101 (Poziotinib) as a therapeutic agent for HER2-overexpressed recurrent stage IV breast cancer, patients who have received at least two prior HER2-directed regimens will be enrolled in this study. Subjects will receive NOV120101 (Poziotinib) 12 mg PO once daily for 2 weeks followed by 1-week drug-free intervals between cycles 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 12 weeks, ORR, DCR, OS and TTP will also be analyzed.

• NOV120101 (Poziotinib) (Drug), also known as HM781-36B, Poziotinib: NOV120101 (Poziotinib) 12 mg PO once daily for 2 weeks followed by a 1-week drug-free interval between cycles until disease progression or unacceptable toxicity development

Primary outcomes

• Progression free survival (PFS) [By 12 months after enrollment of the last subject]

Secondary outcomes

• PFS rate at Week 12 [12 weeks]
• Objective Response Rate (ORR) [By 12 months after enrollment of the last subject]: the proportion of patients with complete response (CR) and/or partial response (PR)
• Disease Control Rate (DCR) [By 12 months after enrollment of the last subject]: the proportion of patients with CR, PR and/or stable disease (SD)\] \[Safety Issue?
• Duration of Disease Control [By 12 months after enrollment of the last subject]
• Overall Survival (OS) [By 12 months after enrollment of the last subject]
• Time To Progression (TTP) [By 12 months after enrollment of the last subject]
• Time to objective response [By 12 months after enrollment of the last subject]
• Duration of objective response [By 12 months after enrollment of the last subject]

Other outcomes

• Population pharmacokinetics (PK) of NOV120101 (Poziotinib) - Ka, CL(clearance), Vd(volume of distribution) [4 weeks]
• Number of Participants with Adverse Events as a Measure of Safety and Tolerability [2 years]

Sex: All, ages: 19 Years to any

Inclusion Criteria:

1. Who give agreement to the collection of tumor tissue specimen suitable for biomarker research
2. ECOG performance status ≤ 2
3. Who received following treatments as Taxane-based chemotherapy and at least two HER2-targeted* therapy including Trastuzumab.

   * lapatinib, T-DM1 (trastuzumab emtansine), pertuzumab
4. Adequate hematological, hepatic and renal functions

Exclusion Criteria:

1. Who received NOV120101 prior to participation in this study
2. Patients expected to exhibit hypersensitivity to IP or its components
3. Any other concurrent chemotherapies
4. Concurrent or prior radiotherapy within 4 weeks before study participation. However, patients with additional lesions other than the major lesion who completed and recovered from all treatment-related toxicities after radiotherapy in a limited area as a palliative therapy are allowed to participate in the study
5. History of symptomatic or unstable angina and congestive heart failure; arrhythmia requiring medications; or clinically significant myocardial infarction or other cardiac diseases within 6 months before study participation for which any related-significant risks are expected
6. Patients whose left ventricle ejection fraction (LVEF) is below the institutional lower limit of normal. However, if no lower limit of normal is defined in the site, the lower limit or normal is 50%.
7. Concurrent active hepatic or biliary disease (with exception of Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver diseases)
8. History or concurrent ongoing/active infection, or uncontrolled diseases including, but not limited to, psychiatric illness/social situations which may limit the compliance with study procedures
9. Prior chemo-, immuno-, or surgical therapy within 3 weeks, or hormone therapy within 1 week before IP administration
10. History of primary malignancies other than breast cancer.
11. Patients with central nervous system (CNS) metastases.
12. Patients receiving or expected to receive bisphosphonate for prophylactic use without any bone-related diseases during the trial, for the exception of the treatment for bone metastases or osteoporosis initiated prior the IP administration.
13. Clinically significant or recent acute gastrointestinal disorders with diarrhea as a major symptom
14. Who are unstable or with unresolved severe adverse event(s)
15. Pregnancy or breast-feeding
16. Women of childbearing potential 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

• Results publication: Kim JY, Park K, Im SA, Jung KH, Sohn J, Lee KS, Kim JH, Yang Y, Park YH. Clinical implications of HER2 mRNA expression and intrinsic subtype in refractory HER2-positive metastatic breast cancer treated with pan-HER inhibitor, poziotinib. Breast Cancer Res Treat. 2020 Dec;184(3):743-753. doi: 10.1007/s10549-020-05891-0. Epub 2020 Aug 28. PMID 32860168