Phase 2 Study of Poziotinib in Patients With NSCLC Having EGFR or HER2 Exon 20 Insertion Mutation

The Screening period (Day -30 to Day -1) lasts up to approximately 30 days prior to Cycle 1,
Day 1. Patients must meet all Inclusion/Exclusion Criteria to participate in the study.
Eligible patients will provide written Informed Consent prior to undergoing any study
procedures.

Each treatment cycle is 28 calendar days in duration. There will be four patient cohorts and
eligible patients will be enrolled into each cohort in parallel based on EGFR or HER2 exon 20
mutation status and prior treatment status:

- Cohort 1: Previously treated patients with EGFR exon 20 insertion mutation positive
NSCLC

- Cohort 2: Previously treated patients with HER2 exon 20 insertion mutation positive
NSCLC

- Cohort 3: Treatment naïve patients with EGFR exon 20 insertion mutation positive NSCLC

- Cohort 4: Treatment naïve patients with HER2 exon 20 insertion mutation positive NSCLC

Toxicity will be assessed based on the grade of the adverse events using CTCAE version 4.03.

All treatments will be taken orally, once daily (QD) at approximately the same time each
morning. On Day 1 of each 28-day cycle, the patient's absolute neutrophil count (ANC) must be
≥1.5×10^9/L and platelet count must be ≥100×10^9/L before administering poziotinib. All
patients will be treated until disease progression, death, intolerable adverse events, or
other protocol-specified reasons for patient withdrawal.

Key Inclusion Criteria:

- Patient must be willing and capable of giving written Informed Consent, adhering to
dosing and visit schedules, and meeting all study requirements

- Patient has histologically or cytologically confirmed locally advanced or metastatic
non-small cell lung cancer (NSCLC) that is not amenable to treatment with curative
intent

- Prior treatment status:

- Cohorts 1 and 2: Patient has had at least one prior systemic treatment for
locally advanced or metastatic NSCLC

- Cohorts 3 and 4: Patient is treatment-naïve for locally advanced or metastatic
NSCLC and eligible to receive first-line treatment with poziotinib as determined
by the Investigator. Adjuvant/neo-adjuvant therapies (chemotherapy, radiotherapy,
or investigational agents) are permissible as long as they end at least 15 days
prior to study entry.

- Specific mutations:

- Cohort 1 and 3: Documented EGFR exon 20 insertion mutation

- Cohort 2 and 4: Documented HER2 exon 20 insertion mutation

- Patient has adequate organ function at Baseline

Key Exclusion Criteria:

- Patient has had previous treatment with poziotinib or any other EGFR or HER2 exon 20
insertion mutation-selective tyrosine kinase inhibitor (TKI) prior to study
participation. The currently approved TKIs (ie, erlotinib, gefitinib, afatinib,
osimertinib) are not considered to be exon 20 insertion-selective and are permissible.

- Patient has had radiotherapy (intention for cure) or surgery (other than surgical
placement for vascular access and minimally invasive procedures including some biopsy
procedures) within 2 weeks prior to start of study treatment with poziotinib

- Patient has had other malignancies within the past 3 years, except for stable
non-melanoma skin cancer, fully treated and stable early stage prostate cancer or
carcinoma in situ of the cervix or breast without need of treatment

- Patient is pregnant or breast-feeding