A Study of Poziotinib in Patients With Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Activating Mutations in Advanced Malignancies

The Screening period (Day -30 to Day 1) begins 30 days prior to poziotinib treatment on Day 1 of Cycle 1. Patients must meet all Inclusion/Exclusion Criteria and provide informed written consent prior to study procedures. The duration of each treatment cycle is 28 days. There will be five patient cohorts. Eligible patients will be enrolled into cohorts concurrently based on EGFR or HER2 exon 20 mutation status. * Cohort 1: HER2-positive or HER2-negative breast cancer (BC) with a HER2 activating mutation. * Cohort 2: Colorectal cancer (CRC) with a HER2 activating mutation. * Cohort 3: Any solid cancer, except non-small cell lung cancer (NSCLC), BC, or CRC with a HER2 activating mutation. * Cohort 4: Glioblastome multiforma (GBM) with an EGFR activating mutation. * Cohort 5: Any solid cancer, except NSCLC or GBM with an EGFR activating mutation. All patients will be treated daily for up to 24 months unless there is disease progression, death, intolerable adverse events (AEs), or another protocol-specified reason for patient withdrawal. After treatment discontinuation, patients will be contacted every 3 months for up to 2 years after the first dose of poziotinib to assess survival.