Phase II Study to Assess the Efficacy of ASLAN001 Plus Capecitabine in CNS Metastases for HER2+ Breast Cancer

Inclusion Criteria:

1. Patients with documented histological confirmation of breast cancer with HER-2 overexpression or gene amplification (immunohistochemistry 3+ or immunohistochemistry 2+ with fluorescent / chromogenic / silver in situ hybridization +) prior to study entry.
2. Patients with HER-2-positive breast cancer with brain metastasis (BMBC) who received either radiosurgery and/or WBRT and progressing in CNS.
3. Presence of more than one radiographically measurable brain metastasis.
4. Patients must complete radiation treatment with either whole brain radiotherapy (WBRT) and/or radiosurgery at least 30 days 30 days prior to study entry. (No washout period for other antineoplastic treatment)
5. Patients must be of legal age of more than 21 years old at the time of written informed consent.
6. Patients of childbearing potential to use adequate contraception prior to, during the study, and 12 weeks after the last dose of therapy.
7. Patients able to understand and willing to sign the informed consent form.
8. Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
9. Patients with acceptable organ and hematological function:

   1. Hematological function:

      * Absolute neutrophil count ≥1.5 × 10\*\*9/L.
      * Platelet count ≥100 × 10\*\*9/L.
      * Hemoglobin ≥9 g/L.
   2. Renal functions:

      \- Serum creatinine ≤1.5 × upper limit of normal (ULN).
   3. Hepatic function:

      * Total bilirubin ≤1.5 × ULN.
      * AST and ALT ≤2.5 × ULN (≤5 × ULN if liver metastases are present).

Exclusion Criteria:

1. Patients with malabsorption syndrome, diseases significantly affecting gastrointestinal function, resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications.
2. Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, diabetes, hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
3. Patients with any history of other malignancy unless in remission for more than 1 year. (Nonmelanoma skin carcinoma and carcinoma-in-situ of uterine cervix treated with curative intent is not exclusionary).
4. Patients who are pregnant or breast-feeding.
5. Patients who were previously treated with ASLAN001 and/or with lapatinib and/or with capecitabine.
6. Patient with known active infection on hepatitis B and hepatitis C and dihydropyrimidine dehydrogenase (DPD) deficiency. (Screening tests not required.)
7. Patients with non-measurable disease alone (i.e. leptomeningeal disease)
8. Patients who need continuous treatment with proton pump inhibitors during the study period.