This phase I/II trial studies the best dose of selumetinib and how well it works with
durvalumab and tremelimumab in treating participants with stage IV non-small cell lung cancer
or that has come back. Immunotherapy with monoclonal antibodies, such as durvalumab and
tremelimumab, may help the body's immune system attack the cancer, and may interfere with the
ability of tumor cells to grow and spread. Selumetinib may stop the growth of tumor cells by
blocking some of the enzymes needed for cell growth. Giving durvalumab, tremelimumab and
selumetinib may work better in treating participants with non-small lung cancer.
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
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.
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
After completion of study treatment, participants are followed up at 30 and 90 days, then
every 6 months for up to 2 years.
Recurrent Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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