Poziotinib in EGFR Exon 20 Mutant Advanced Non-Small Cell Lung Cancer (NSCLC) and HER2 Exon 20 Mutant NSCLC

Inclusion Criteria:

1. Histologically or cytologically confirmed stage IV or recurrent solid tumor not
amenable to curative intent therapy.

2. Cohort 1 specific inclusion criteria: Documented EGFR exon 20 mutation by one of the
following CLIA certified tests: OncoMine Comprehensive Assay (OCA), Guardant360 Assay
(using plasma), or FoundationOne Assay or by an FDA approved device using cobas® EGFR
mutation test v2 or therascreen EGFR RGQ PCt kit. Eligible mutations include
A763_Y764insFQEA, D770_N771insSVD, D770_N771insNPG, V769_D770insASV, H773_V774insNPH,
or any other exon 20 in-frame insertion or point mutation excluding T790M.

3. Patients must be previously treated with one or more regimens of systemic therapy for
locally advanced or metastatic disease. Previously untreated patients are eligible
only if EGFR Exon 20 mutation is confirmed using an FDA approved device: cobas® EGFR
Mutation Test v2 or therascreen® EGFR RGQ PCR Kit prior to study enrollment.

4. Cohort 2 specific inclusion criteria: Documented HER2 exon 20 mutation by a CLIA
certified laboratory. Eligible mutations include A775_G776insYVMA, G776_V777insVC, or
P780_Y781insGSP, or any other in-frame exon 20 insertion mutation or point mutation
including, but not limited to, L755S, G776V, and V777L.

5. Measurable disease by RECIST 1.1.

6. Age >/= 18 years.

7. ECOG performance status 0 or 1.

8. Ability to take pills by mouth

9. Patients must have normal organ and marrow function as defined below: leukocytes >/=
3,000/mcL; absolute neutrophil count >/= 1,500/mcL; platelets >/= 100,000/mcL;
hemoglobin >/= 9.0 g/dL; total bilirubin AST(SGOT)/ALT(SGPT)/Alkaline phosphatase of /50 mL/min/1.73
m^2 by Cockcroft-Gault equation (creatinine clearance = ([140-age] x body mass/(plasma
creatinine x 72) x gender correction factor) or by 24-hours urine collection

10. Brain metastases are allowed, as long as they are stable and do not require treatment
with anticonvulsants or escalating doses of steroids.

11. Females of childbearing potential must have a negative serum or urine pregnancy test
and must agree to use adequate contraception for the duration of the study and six
months after. Adequate contraception methods include: birth control pills (eg combined
oral contraceptive pill), barrier protection (eg condom plus spermicide,
cervical/vault or intrauterine device), and abstinence. Females of childbearing
potential are defined as those who are not surgically sterile (ie, bilateral tubal
ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined
as 12 months with no menses without an alternative medical cause). Women will be
considered post-menopausal if they have been amenorrheic for the past 12 months
without an alternative medical cause. Inclusion Criterion cont'd in # 12.

12. Continuation from inclusion criterion # 11: The following age-specific requirements
must also apply: Women < 50 years old: they would be considered post-menopausal if
they have been amenorrheic for the past 12 months or more following cessation of
exogenous hormonal treatments. The levels of Luteinizing Hormone (LH) and
Follicle-Stimulating Hormone (FSH) must also be in the post-menopausal range (as per
the institution). Women >/= 50 years old: they would be considered post-menopausal if
they have been amenorrheic for the past 12 months or more following cessation of all
exogenous hormonal treatments, or have had radiation-induced oophorectomy with the
last menses > 1 year ago, or have had chemotherapy-induced menopause with > 1 year
interval since last menses, or have had surgical sterilization by either bilateral
oophorectomy or hysterectomy.

13. Non-sterilized males who are sexually active with a female partner of childbearing
potential must use adequate contraception for the duration of the study and 90 days
after the last dose of study medication. Adequate contraception methods include: birth
control pills (eg combined oral contraceptive pill), barrier protection (eg condom
plus spermicide, cervical/vault cap or intrauterine device), and abstinence.

14. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. EGFR T790M mutation or any other acquired EGFR exon 20 mutation. Patients with
coexisting primary EGFR exon 20 and T790M mutations are eligible.

2. Have received or are receiving an investigational medicinal product (IMP) or other
systemic anticancer treatment within 2 weeks prior to the first dose of study
treatment.

3. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer
treatment.

4. Have known or suspected brain metastases or spinal cord compression, unless the
condition has been asymptomatic, has been treated with surgery and/or radiation, and
has been stable without requiring escalating corticosteroids nor anti-convulsant
medications for at least 4 weeks prior to the first dose of study medication.

5. Known hypersensitivity to poziotinib or history of allergic reactions attributed to
compounds of similar chemical or biologic composition to poziotinib.

6. Cardiac conditions as follows: Patient has a history of congestive heart failure (CHF)
Class III/IV according to the New York Heart Association (NYHA) Functional
Classification or serious cardiac arrhythmias requiring treatment. Patient has a
cardiac ejection fraction <50% by either echocardiogram or multi-gated acquisition
(MUGA) scan

7. Have any unresolved chronic toxicity with CTCAE version 4.03 Grade >/= 2, from
previous anticancer therapy, except for alopecia.

8. Patient is unable to take drugs orally due to disorders or diseases that may affect
gastrointestinal function, such as inflammatory bowel diseases (eg, Crohn's disease,
ulcerative colitis) or malabsorption syndrome, or procedures that may affect
gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.

9. Have any condition or illness that, in the opinion of the investigator, might
compromise patient safety or interfere with the evaluation of the safety of the drug

10. Pregnant or breastfeeding women

11. History of another primary malignancy within 2 years prior to starting study
treatment, except for adequately treated basal or squamous cell carcinoma of the skin
or cancer of the cervix in situ

12. Recent major surgery within 4 weeks prior to starting study treatment, with the
exception of surgical placement for vascular access

13. Male or female patients of reproductive potential who are not employing an effective
method of birth control. Adequate contraception methods include: birth control pills
(eg combined oral contraceptive pill), barrier protection (eg condom plus spermicide
cervical/vault cap or intrauterine device), and abstinence.

14. Uncontrolled intercurrent illness including, but not limited to, uncompensated
respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis
B, hepatitis C, HIV, and active clinical tuberculosis), or renal transplant; ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric
illness/social situations that would limit compliance with study requirements.

15. Active bleeding disorders.