A Study Osimertinib in Patients With Stage 4 Non-small Cell Lung Cancer With Uncommon EGFR Mutations

Inclusion Criteria: * EGFR mutations as performed on a CLIA certified laboratory demonstrating EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q. Patients with compound (also referred to as multiple mutations) will be eligible provided the NSCLC demonstrates one of these mutations). * Histological or cytological confirmation diagnosis of Stage 4 NSCLC. * Measurable disease by RECIST 1.1 (please refer to appendix 4) * The following laboratory values obtained ≤ 14 days prior to study initiation. * Hematology: ANC ≥ 1, 500 / ml, platelet count, ≥ 100,000 / ml, hemoglobin ≥ 9.0 g / dl * Hepatic:ALT or ALT \< 2.5 times ULN if no demonstrable liver metastases or \<5 times ULN in the presence of liver metastases * Total bilirubin \< 1.5 times ULN if no liver metastases or \< 3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases * Renal: Cockcroft-Gault calculated creatinine clearance of ≥ 45 ml/min or creatinine ≤1.5 x ULN * Have normal QT interval on ECG evaluation QT corrected of ≤ 450 ms in males or ≤ 470 ms in females obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine-derived QTc value * Cardiac ejection fraction of ≥ 45% * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or1 * Negative pregnancy test done ≤7 days (or per institutional policy) prior to treatment, for women of childbearing potential only. Female must use highly effective contraceptive measures, and must have a negative pregnancy test or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: * Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments. * Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution * Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation * Male subjects must be willing to use barrier contraception * Age ≥ 18 years * Provision of written informed consent prior to any study-specific procedures Exclusion Criteria: * Prior therapy with EGFR TKI therapy * Greater than 2 lines of prior systemic therapy for metastatic non-small cell lung cancer. * Any cytotoxic chemotherapy or other anticancer drugs from previous treatment regimen or clinical study within 14 days of first dose of study drug. * Treatment with an investigational drug within 5 half-lives of the compound * Other active malignancy ≤ 2 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history of prior malignancy, patients must not be receiving other specific treatment (i.e. hormonal therapy) for their cancer * Prior radiotherapy ≤ 14 days * Untreated symptomatic brain metastases (treated brain metastases are allowed provided \> 14 days have elapsed from completion of radiotherapy and patient is neurologically stable as assessed by treating physician). * Malabsorption syndrome, refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib * Detection of concurrent EGFR mutation with exon 20 T790M, exon 19 deletion, exon 21 L858R mutation or exon 20 insertion. Patients with compound (also referred to as multiple mutations) will be excluded if the molecular testing includes one of these mutations. * Active pregnancy or breast-feeding: Pregnant women are excluded from this study because the effects of osimertinib on the development of the fetus are unknown, and there is potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with osimertinib, breastfeeding should be discontinued if the mother is treated with these agents. * Grade ≥ 2 blurred vision, conjunctivitis, corneal ulcer, dry eye, or keratitis