Background: EGFR tyrosine kinase inhibitors (TKI) are the recommended first line treatment for EGFR-mutant lung cancers. Osimertinib, an EGFR TKI that inhibits both sensitizing EGFR mutations and EGFR T790M, is approved for use after progression on an EGFR TKI with evidence of EGFR T790M, and is currently being assessed as initial treatment for EGFR-mutant lung cancers. The addition of bevacizumab to erlotinib resulted in improved progression free survival (PFS) compared to erlotinib alone as initial treatment (16 vs 10 months, HR 0.41). This phase 1/2 study is assessing osimertinib and bevacizumab as initial treatment for patients with EGFR-mutant lung cancers. Methods: We evaluated toxicity and efficacy of osimertinib and bevacizumab as initial treatment for patients with advanced EGFR-mutant lung cancers. Using a 3+3 design, full doses of osimertinib (80mg PO daily) and bevacizumab (15mg/kg IV q3 weeks) were given, with a planned dose de-escalation (osimertinib 40mg PO daily) should grade 3 or greater toxicity be seen. Six patients must be treated without a dose-limiting toxicity (DLT) to determine the MTD. 43 additional patients will be treated at the MTD in the phase 2 study, with a primary endpoint of PFS at 12 months. Response was evaluated by RECIST 1.1. Results: From Sept 2016 to Jan 2017, 15 patients were enrolled. Median age: 63; Women 11; EGFR L858R = 8, Ex19del = 6, G709A/G719S = 1. After median duration of treatment of 2.7 months, no DLTs were seen in any patient. The MTD was determined to be osimertinib 80mg, bevacizumab 15mg/kg q3 weeks. In total, 15 patients are being treated at the MTD to date. Treatment-related adverse events (AE) were all grade 1-2, except for grade 3 hypertension. The most frequent treatment-related AEs (any grade) were rash (53%), diarrhea (40%), hypertension (33%), fatigue (20%), and itching (20%). All 15 patients continue on study. Conclusions: Combination osimertinib and bevacizumab is a tolerable first-line treatment for patients with EGFR-mutant lung cancers and the MTD is osimertinib 80mg and bevacizumab 15mg/kg q3 weeks. Assessment of efficacy with an endpoint of PFS at 12 months is ongoing. Supported by AstraZeneca (NCT02803203). Clinical trial information: NCT02803203