Durvalumab, Tremelimumab, and Selumetinib in Treating Participants With Recurrent or Stage IV Non-small Cell Lung Cancer

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD). (Dose-escalation phase) II. To estimate the progression free survival in patients with previously treated non-small cell lung cancer (NSCLC) treated with durvalumab and tremelimumab in combination with selumetinib in either an intermittent or continuous schedule and compare to historical controls. (Dose expansion phase) SECONDARY OBJECTIVES: I. To assess response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. II. To assess disease control rate (complete response + partial response + stable disease). III. To assess overall survival. IV. To assess safety and toxicity (in the dose-escalation and dose expansion phases). V. To assess duration of response. EXPLORATORY OBJECTIVES: I. To assess markers of response and resistance in pre-treatment and on- treatment biopsies. OUTLINE: This is a phase I, dose-escalation study of selumetinib followed by a phase II study. Participants are randomized to 1 of 2 arms. ARM I: Participants receive selumetinib orally (PO) twice daily (BID) on days 1-7 and 15-21 and durvalumab intravenously (IV) over 60 minutes on day 1. Participants also receive tremelimumab IV over 60 minutes on day 1 for courses 1-4. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Participants receive selumetinib PO BID on days 1-28 and durvalumab IV over 60 minutes on day 1. Participants also receive tremelimumab IV over 60 minutes on day 1 for courses 1-4. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 30 and 90 days, then every 6 months for up to 2 years.