Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers

Inclusion Criteria: * Written informed consent * Advanced biopsy-proven metastatic non-small cell lung cancer * Somatic activating mutation in EGFR * No prior treatment with an EGFR TKI * No prior treatment with a VEGF inhibitor * Measurable (RECIST 1.1) indicator lesion not previously irradiated * Karnofsky performance status (KPS) ≥ 70% * Age \>18 years old * Adequate organ function * AST, ALT ≤ 3 x ULN * Total bilirubin ≤ 1.5x ULN * Creatinine ≤ 1.5x ULN OR calculated creatinine clearance \> 60ml/min * Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 * Hemoglobin≥8.0 g/dL * Platelets ≥100,000/mm3 Exclusion Criteria: * Any contra-indications to bevacizumab which include but are not limited to recent 1. Any previous venous thromboembolism \> NCI CTCAE Grade 3 2. Severe uncontrolled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥ 100mmHg) 3. Cardiovascular disease including stroke of myocardial infarction \<6 months prior to study enrollment, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrythmia uncontrolled by medication 4. Hemorrhagic brain metastases. Asymptomatic (not requiring escalating doses of steroids) brain metastases are acceptable. 5. History of severe proteinuria (urine dipstick ≥ 2+ or 24 hr urine \> 2gm/24hr) 6. Prior history of hypertensive crisis or hypertensive encephalopathy 7. History of a central nervous system disease (e.g. seizures) unrelated to cancer unless adequately treated with standard medical therapy 8. Significant vascular disease (e.g. aortic aneurysm requiring surgical repair)≥ 6 months prior to study enrollment 9. History of hemoptysis (≥1/2 teaspoon of bright red blood per episode) within the last 3 months 10. Evidence of a bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) 11. Current or recent (within 10 days of study drug start) use of aspirin (\>325mg daily), clopidogrel (\>75mg daily). 12. Recent initiation of full dose oral or parental anticoagulants that have not been in place for at least 2 weeks. 13. Tumor invading or abutting major blood vessels 14. Tumor histology classified by squamous cell histology. 15. Any history of abdominal fistula or GI perforation within 6 months of study enrollment * Pregnant or lactating women * Any type of systemic anticancer therapy (chemotherapy or experimental drugs) within 2 weeks of starting treatment on protocol * Any radiotherapy within 1 week of starting treatment on protocol * Any major surgery within 4 weeks of starting treatment on protocol * Any evidence of clinically significant interstitial lung disease * Known hypersensitivity to any component of bevacizumab and osimertinib