A Phase II, Single-Arm Trial of Poziotinib as Salvage Treatment in Patients With Metastatic Breast Cancer Who Has HER2 or EGFR Mutation or Activated AR or EGFR Pathway

Inclusion criteria

• Histologically confirmed metastatic breast cancer with measurable or evaluable disease
• age ≥ 20 years
• HER2 mutation or EGFR mutation/gene amplification confirmed by CancerSCAN or Activated AR pathway confirmed by RNA seq & nCounter assay, AR expression was confirmed by immunohistochemistry(IHC) or EGFR high expression (≥ IHC 2+ & lower ER / ≥ IHC score + and HER2 2+ or SISH negative)
• ECOG performance status 0 - 2
• Two or more regimens for locally recurrent or metastatic breast cancer, including an anthracycline and a taxane
• Life expectancy ≥ 3 months
• Progression within 6 months or less of latest chemotherapy
• The patients must have recovered from the acute toxic effects of the treatment prior to study enrollment. Prior radiotherapy must be completed 2 weeks before study entry.
• Adequate bone marrow function (≥ ANC 1,500/ul, ≥ platelet 100,000/ul, ≥ Hemoglobin 9.0 g/dl)
• Adequate renal function (serum creatinine ≤ 1.5 x upper normal limit or CCr ≥ 50 ml/min)
• Adequate liver function (serum bilirubin ≤ 1.5 x upper normal limit, AST/ALT ≤ 3 x upper normal limit)
• No prior history of pan-HER TKI including poziotinib for metastatic breast cancer
• Written informed consent

Exclusion criteria

• HER2-overexpressing breast cancer
• Serious uncontrolled intercurrent infections
• Serious intercurrent medical or psychiatric illness, including active cardiac disease
• Pregnancy or breast feeding
• Second primary malignancy(except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or resected thyroid papillary carcinoma or other malignancy treated at least 5 years previously with no evidence of recurrence)
• Documented leptomeningeal brain metastasis
• Known brain metastases unless treated and stable
• Peripheral neuropathy ≥ grade 3
• Prior treatment with pan-HER TKI including poziotinib will not be allowed.
• Use of any investigational drug within 4 weeks of the study
• Treatment with chemotherapy or hormone therapy within 3 weeks of the study