Osimertinib Then Chemotherapy in EGFR-mutated Lung Cancer with Osimertinib Third-line Rechallenge

Inclusion Criteria: * Provision of informed consent prior to any study specific procedures * Male or female patients of at least 18 years of age * Pathologically proven advanced non-small cell lung cancer (i.e. stage M1 (metastasis), or earlier stages if unfit or unsuitable for radical treatment). Patients must have a tissue diagnosis of lung cancer, either by histology or cytology, however, in the event that there is insufficient tissue for molecular analysis, mutations identified in circulating tumor deoxyribonucleic acid (ctDNA) analysis will be permitted. * Patients must have a known activating Epidermal Growth Factor Receptor (EGFR) mutation. Atypical Epidermal Growth Factor Receptor (EGRF) mutations are allowed. Atypical mutations may require sponsor approval. Exon 20 insertions will not be allowed. * Patients must have an Eastern Cooperative Oncology Group/World Health Organisation Performance Status (ECOG/WHO-PS) of 0-3 and an expectation that they could potentially receive second-line chemotherapy * Patients must have an expected life expectancy of at least 12 weeks * Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding 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 amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments * Women under 50 years old are consider postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle Stimulating Hormone (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 should be willing to use barrier contraception * Additional Criteria for patients enrolling after first-line progression and prior to second-line chemotherapy:: * Subjects must have complete baseline demographic data available (age at diagnosis of metastatic non-small cell lung cancer, ethnicity, smoking status, sex, history of brain metastasis) and the following must be available (if applicable): o Date of first dose of osimertinib, date that first-line osimertinib was permanently discontinued, date of first-line progression. * Additional Criteria for patients enrolling at the time of third-line osimertinib rechallenge: * Subjects must have complete baseline demographic data available (age at diagnosis of metastatic non-small cell lung cancer (NSCLC), ethnicity, smoking status, sex, history of brain metastasis) and the following must be available (if applicable): o Date of first dose of osimertinib, date that first-line osimertinib was permanently discontinued, date of first-line progression, date second-line chemotherapy was started, which platinum chemotherapy was given, if pemetrexed maintenance was given, date that second-line chemotherapy was permanently stopped, and date of progression on second-line treatment. * Patients must have received platinum/ pemetrexed chemotherapy in the second-line chemotherapy * Subjects must have measurable disease defined as at least one measurable lesion that can be accurately assessed by Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) at baseline and follow up visits.Subjects must have measurable disease defined as at least one measurable lesion that can be accurately assessed by Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) at baseline and follow up visits. Exclusion Criteria: * Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or involved staff at the study site). * A second invasive malignancy in the previous three years, other than localized non-melanoma skin cancer, which might be confused with the Epidermal Growth Factor Receptor (EGFR) mutated lung cancer. * Any other serious and uncontrolled medical or psychiatric condition which would likely interfere in the conduct of the study. * Pregnancy or lactation * Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater. * Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of Cytochrome P450 3A4 (CYP3A4) (at least 3 weeks prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on Cytochrome P450 3A4 (CYP3A4). * 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. * 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, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. * Patients with spinal cord compression, symptomatic and unstable brain metastases except for those patients who have completed definitive therapy and have had a stable neurological status for at least 2 weeks after completion of definitive therapy. Patients may be on corticosteroids to control brain metastases if they have been on a stable dose for 2 weeks (14 days) prior to the start of study treatment and are clinically asymptomatic. * 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. * Past medical history of Interstitial Lung Disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. * Inadequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values: absolute neutrophil count less than1.5 x 10 to the power of 9/L, platelet count less than 100 x 10 to the power of 9/L, haemoglobin less than 90 g/L), alanine aminotransferase greater than 2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or greater than 5 times ULN in the presence of liver metastases; aspartate aminotransferase greater than 2.5 times ULN if no demonstrable liver metastases or greater than 5 times ULN in the presence of liver metastases; total bilirubin greater than 1.5 times ULN if no liver metastases or greater than 3 times ULN in the presence of documented Gilbert's Syndrome \[unconjugated hyperbilirubinaemia\] or liver metastases; serum creatinine greater than 1.5 times ULN concurrent with creatinine clearance less than 50 mL/min \[measured or calculated by Cockcroft and Gault equation\]-confirmation of creatinine clearance is only required when creatinine is greater than 1.5 times ULN. * History of hypersensitivity to any of the active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib. * 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. * Previous adjuvant cytotoxic chemotherapy within the 6 months prior to enrollment. * Previous adjuvant anti programmed cell death protein 1(anti-PD-1) or anti programmed death-ligand 1 (anti-PD-L1) therapy within 90 days prior to enrollment. * For patients enrolling prior to first-line treatment with osimertinib: * Any previous systemic therapy for Epidermal Growth Factor Receptor mutated (EGFR+) advanced Non-Small Cell Lung Cancer (aNSCLC). * Any of the following cardiac criteria: * Mean resting corrected QT interval (QTc) greater than 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value * Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block. * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities \[including serum/plasma potassium less than the Lower Limit of Normal (LLN), serum/plasma magnesium greater than the Lower Limit of Normal (LLN), serum/plasma calcium less than the Lower Limit of Normal (LLN)\], 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 and cause Torsades de Pointes. * For patients enrolling after progression on first-line osimertinib and prior to second-line chemotherapy all patients must have: * Received osimertinib in the first-line and no other systemic therapy for their Epidermal Growth Factor Receptor mutated (EGFR+) Advanced Non-Small Cell Lung Cancer (aNSCLC). * For patients enrolling at the time of third-line osimertinib rechallenge all patients must have: * Received osimertinib in the first-line followed by second-line platinum (carboplatin/cisplatin) with pemetrexed (pemetrexed maintenance is permitted), and no other systemic therapy for their Epidermal Growth Factor Receptor mutated (EGFR+) advanced Non-Small Cell Lung Cancer. * Received a minimum of 1 dose of platinum (carboplatin/cisplatin) with pemetrexed. * AND * At least 90 days have lapsed since the last dose of first-line osimertinib.