A Study of Poziotinib in Previously Treated Participants With Locally Advanced or Metastatic NSCLC Harboring HER2 Exon 20 Mutations

Participant must: 1. Be willing and capable of providing signed and dated Informed Consent, adhering to dosing and visit schedules, and meeting the study requirements 2. Have histologically or cytologically confirmed NSCLC 3. Have at least one measurable NSCLC target lesion per RECIST v.1.1 by local assessment 4. Participant has had at least one prior systemic treatment for locally advanced or metastatic NSCLC, including platinum and a checkpoint inhibitor (CPI) therapy, unless the investigator affirms that a CPI was not medically indicated. 5. Have documentation of HER2 exon 20 mutation 6. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 7. Have adequate hematologic, hepatic, and renal function at Baseline as per protocol

Participant: 1. Has had previous treatment with poziotinib for treatment of NSCLC 2. Has EGFR or anaplastic lymphoma kinase (ALK) genome tumor alterations 3. Has had previous treatment with docetaxel for locally advanced or metastatic NSCLC. If docetaxel was received in the neo-adjuvant or adjuvant setting, progressive disease must have occurred ≥6 months after the last dose to be eligible 4. Has spinal cord compression or leptomeningeal disease 5. Has a high risk of cardiac disease, as determined by the Investigator 6. Has a history of, or signs of Grade ≥2 pneumonitis on current imaging studies 7. Is unable to take drugs orally 8. Is pregnant or breast-feeding