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.