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

This is a Phase 3, active-controlled, multicenter study to compare the efficacy and safety/tolerability of poziotinib versus docetaxel in previously treated participants with locally advanced or metastatic NSCLC harboring HER2 exon 20 mutations.

Participants will be randomized in a 2:1 ratio to:

• Arm A: Poziotinib 8 milligrams (mg), twice daily (BID) or
• Arm B: Docetaxel 75 milligrams per meter square (mg/m^2)

The Screening Period lasts up to 21 days prior to Cycle 1, Day 1 (C1D1). Participants will be treated in 21-day cycles or until disease progression, death, intolerable adverse events (AEs), initiation of non-protocol anti-cancer treatment, or other protocol-specified reasons.

Inclusion criteria

Participant must:

• Be willing and capable of providing signed and dated Informed Consent, adhering to dosing and visit schedules, and meeting the study requirements
• Have histologically or cytologically confirmed NSCLC
• Have at least one measurable NSCLC target lesion per RECIST v.1.1 by local assessment
• 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.
• Have documentation of HER2 exon 20 mutation
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Have adequate hematologic, hepatic, and renal function at Baseline as per protocol

Exclusion criteria

Participant:

• Has had previous treatment with poziotinib for treatment of NSCLC
• Has EGFR or anaplastic lymphoma kinase (ALK) genome tumor alterations
• 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
• Has spinal cord compression or leptomeningeal disease
• Has a high risk of cardiac disease, as determined by the Investigator
• Has a history of, or signs of Grade ≥2 pneumonitis on current imaging studies
• Is unable to take drugs orally
• Is pregnant or breast-feeding