-  INCLUSION CRITERIA:

        For inclusion in the study subjects should fulfill the following criteria:

          -  Provision of informed consent prior to any study specific procedures

          -  Patients (male/female) must be greater than or equal to 18 years of age.

          -  Patients with histologically confirmed, by the NCI Laboratory of Pathology or by
             CLIA-certified Next Generation Sequencing or cobas EGFR Mutation Test v1/2 at an
             outside institution, advanced lung adenocarcinoma with EGFR-sensitizing somatic
             mutations or a germline T790M mutation (detected histologically or via ctDNA analysis
             using a CLIA assay) with:

               -  No prior EGFR tyrosine kinase inhibitor (TKI) therapy (Cohort 1)

        OR

        -- Progressive disease after 1st or 2nd generation EGFR TKI therapy harboring somatic T790M
        mutation (Cohort 2)

        OR

          -  Progressive disease after treatment with osimertinib who are eligible for local
             ablative therapy (Cohort 3)

               -  Presence of measurable disease per RECIST version 1.1.

               -  In patients with suspected leptomeningeal disease, the diagnosis of
                  leptomeningeal disease should be confirmed by the presence of neurological or
                  imaging signs and/or positive CSF cytology.

               -  ECOG performance status 0-2.

               -  No uncontrolled arrhythmia; no myocardial infarction in the last 6 months.

               -  Females should not be breast feeding and must have a negative pregnancy test
                  prior to start of dosing if of child-bearing potential 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 consider 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

               -  Females of child-bearing potential should use reliable methods of contraception
                  from the time of screening until 3 months after discontinuing osimertinib.
                  Acceptable methods of contraception include total and true sexual abstinence,
                  tubal ligation, hormonal contraceptives that are not prone to drug-drug
                  interactions (IUS Levonorgestrel Intra Uterine System (Mirena),
                  Medroxyprogesterone injections (Depo-Provera), copper-banded intra-uterine
                  devices, and vasectomized partner. All hormonal methods of contraception should
                  be used in combination with the use of a condom by their male sexual partner for
                  intercourse.

               -  Male patients should be willing to use barrier contraception. Male patients
                  should be asked to use barrier contraceptives (i.e., by use of condoms) during
                  sex with all of their female partners during the trial and for a washout period
                  of 3 months. Patients should refrain from donating sperm from the start of dosing
                  until 6 months after discontinuing osimertinib treatment. If male patients wish
                  to father children they should be advised to arrange for freezing of sperm
                  samples prior to the start of osimertinib treatment.

               -  Patient is willing and able to comply with the protocol for the duration of the
                  study including undergoing treatment and scheduled visits and examinations
                  including follow up.

        EXCLUSION CRITERIA:

        Subjects should not enter the study if any of the following exclusion criteria are
        fulfilled:

          -  Any unresolved toxicities from prior therapy greater than Common Terminology Criteria
             for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the
             exception of alopecia and grade 2, prior platinum-therapy related neuropathy.

          -  Treatment with an investigational drug within five half-lives of the compound.

          -  Major thoracic or abdominal surgery from which the patient has not sufficiently
             recovered yet.

          -  Untreated and uncontrolled second tumor in the past 2 years.

          -  Patients currently receiving (or unable to stop use prior to receiving the first dose
             of study treatment) medications or herbal supplements known to be potent inhibitors of
             CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior)
             will only be eligible at the PI s discretion.

          -  Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
             hypertension and active bleeding diatheses, which in the investigator s opinion makes
             it undesirable for the patient to participate in the trial or which would jeopardize
             compliance with the protocol. Screening for chronic conditions is not required.

          -  Patients with CNS metastases who are neurologically unstable.

          -  Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation
             pneumonitis requiring steroid treatment, or any evidence of clinically active ILD

          -  Inadequate bone marrow reserve or organ function as demonstrated by any of the
             following laboratory values:

               -  Absolute neutrophil count <1 x 10(9)/L

               -  Platelet count <100 x 10(9)/L

               -  Hemoglobin <90 g/L

               -  Alanine aminotransferase >2.5 times the 2.1.2.9.4 upper limit of normal (ULN) if
                  no demonstrable liver metastases or >5 times ULN in the presence of liver
                  metastases

               -  Aspartate aminotransferase >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 hyperbilirubinemia) or
                  liver metastases

               -  Creatinine >1.5 times ULN concurrent with creatinine clearance <30 ml/min
                  (measured or calculated by Cockcroft and Gault equation); confirmation of
                  creatinine clearance is only required when creatinine is >1.5 times ULN

          -  Any of the following cardiac criteria

               -  Resting corrected QT interval (QTc using Fredericia s formula) > 480 msec

               -  Any clinically important abnormalities in rhythm, conduction or morphology of
                  resting ECG (e.g., complete left bundle branch block, third degree heart block,
                  second degree heart block)

               -  Any factors that increase the risk of QTc prolongation or risk of arrhythmic
                  events such as heart failure, hypokalemia, congenital long QT syndrome, family
                  history of long QT syndrome or unexplained sudden death under 40 years of age in
                  first degree relatives or any concomitant medication known to prolong the QT
                  interval

               -  Significant symptomatic congestive heart failure, per PI judgement.

          -  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

          -  History of hypersensitivity to osimertinib (or drugs with a similar chemical structure
             or class to osimertinib) or any excipients of these agents

          -  Judgment by the Investigator that the patient should not participate in the study if
             the patient is unlikely to comply with study procedures, restrictions and requirements