Advanced Lung Tumor Treated by Osimertinib Plus Anlotinib

Inclusion Criteria: * For inclusion in the study subjects should fulfil the following criteria: 1. Provision of informed consent prior to any study specific procedures. 2. Aged at least 18 years. 3. Histologically or cytologically confirmed locally advanced/metastasis NSCLC, adenocarcinoma of the lung (AJCC Eighth Edition TNM Stage ⅢB to stage Ⅳ), not amenable to curative surgery or radiotherapy. 4. WHO/Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 with no deterioration over the previous 2 weeks and a minimum life expectation of at least 12 weeks. 5. The tumour harbours one of the most common EGFR mutations known to be associated with EGFR-TKI sensitivity (exon 19 deletion; L858R) either alone or in combination with other EGFR mutations as confirmed by a local test. 6. No prior systemic anti-cancer, EGFR-TKI, or immunotherapy therapy for their locally advanced or metastasis disease (biopsy will be at time of diagnosis of locally advanced/metastasis disease). 7. At least one lesion is measurable based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1). 8. Adequate bone marrow reserve and organ function as follows: * Absolute neutrophils count (ANC) ≥1.5x109/L (band neutrophil and segmented neutrophil), platelets \>100x109/L and Hb ≥90g/L. * Hepatic: total bilirubin ≤1.5 times upper limit of normal (ULN). * Alkaline phosphatase, alanine transaminase (ALT) and aspartate transaminase (AST)≤3.0 ULN (or ≤5 ULN in case of known liver involvement). * Renal: Serum Creatinine ≤1.5ULN, creatinine clearance (CCr) ≥50mL/min 9. Female patients of childbearing potential must be using adequate contraceptive measures (see Restrictions, Section3.5), must not be breast feeding, and must have a negative pregnancy test prior of study treatments and confirmed prior to start of dosing on day 1. Otherwise, they must have evidence of non-childbearing potential as defined below: * 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 would be consider post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution * Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation 10. Male patients must be willing to use barrier contraception, i.e., condoms (see Restrictions, Section 3.5) 11. Optional provision of an unstained, archived tumour tissue samples or fresh tissue and/or blood in a quantity sufficient to allow for central NGS testing (FFPE slices or fresh tumor tissue or blood at sufficient amount for NGS analysis). Exclusion Criteria: \- Subjects must not enter the study if any of the following exclusion criteria are fulfilled: 1. Patients with non-lung adenocarcinoma including lung squamous carcinoma, or mixed histology, etc. 2. Treatment with any of the following: * Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug. * Patients currently receiving (or unable to stop use prior to receiving the first dose of study drug) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3-week prior) (Appendix B). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4. * Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater. 3. Any concurrent and/or other active malignancy that has required treatment within 5 years of first dose of study drug. 4. Any unresolved toxicities from prior systemic therapy (e.g., adjuvant chemotherapy) greater than CTCAE grade 1 at the time of starting study drug with the exception of alopecia and grade 2, prior chemotherapy-induced neuropathy. 5. 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. 6. 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 jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. 7. Recent active digestive disease such as duodenal ulcers, ulcerative colitis, ileus, ect., intestinal perforation, intestine fistula, or other conditions may lead to gastrointestinal bleeding or perforation which regimented at investigators' discretion. 8. 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 and Anlotinib. 9. Cardiac function evaluation: LVEF \<50%, a recent history of MI in 6 months, severe/unstable angina or coronary bypass surgery, or cardiac insufficiency ≥ NYHA 2. Any of the following cardiac criteria: * Mean resting corrected QT interval (QTc) \>470 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, interval \>250 msec. * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/plasma potassium \< LLN; Serum/plasma magnesium \< LLN; Serum/plasma calcium \< 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. * Past medical history of ILD, drug-induced ILD, radiation pneumonitis which require steroid treatment, or any evidence of clinically active ILD. * Previous allogenic bone marrow transplant. * Pregnant or lactating woman who are breast feeding. * A history of organ transplantation and long-term immunosuppressive medication. * History of hypersensitivity to active or inactive of Osimertinib or Anlotinib or drugs with a similar chemical structure or class to osimertinib or Anlotinib. 10. Judgment by the Investigator that the patients should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.; or other conditions regimented at investigators' discretion.