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

Primary Outcome Measures

• Objective Response Rate (ORR) to Poziotinib in Non-Small Cell Lung Cancer (NSCLC) Participants with EGFR Exon 20 Mutations [ Time Frame: 3 months ].ORR calculated as the percent of patients whose best confirmed response is complete response (CR, defined as disappearance of all target lesions) or partial response (PR, defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD). ORR assessed according to RECIST 1.1 criteria.
• Adverse Events of Poziotinib in Non-Small Cell Lung Cancer (NSCLC) Participants with EGFR Exon 20 Mutations [ Time Frame: 1 month ]. Adverse events assessed by Common Terminology Criteria for Adverse Events version 4.03.

Secondary Outcome Measures

Disease Control Rate of Poziotinib in Non-Small Cell Lung Cancer (NSCLC) Participants with EGFR Exon 20 Mutations [ Time Frame: 8 weeks after initiation of treatment. ].Disease control rate defined as the percentage of patients have either a partial response (PR), a complete response (CR), or stable disease (SD) lasting at least 8 weeks after initiation of treatment. Response assessed by RECIST 1.1 criteria.

Eligibility

Inclusion Criteria

Histologically or cytologically confirmed recurrent non-small cell lung cancer not amenable to curative intent therapy or stage IV NSCLC

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. Mutations include D770_N771insSVD, D770_N771insNPG, V769_D770insASV, H773_V774insNPH, or any other exon 20 in-frame insertion or point mutation excluding T790M.

Patients must have progression of disease on or after a platinum-containing regimen. Multiple lines of therapy are allowed as long as previous therapy includes a platinum-containing regimen.

Measurable disease by RECIST 1.1.

Adequate tumor tissue obtained from a biopsy or surgical procedure to enable molecular profiling. If tissue is not available, the patient must have biopsy accessible disease and must be willing to undergo a biopsy.

Age >/= 18 years.

ECOG performance status 0 or 1.

Ability to take pills by mouth

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 /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

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

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.

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.

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.

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

Exclusion Criteria

EGFR T790M mutation or any other acquired EGFR exon 20 mutation

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.

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

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.

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

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

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

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.

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

Pregnant or breastfeeding women

History of another primary malignancy within 5 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

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

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.

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), active bleeding diatheses 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.