PRIMARY OBJECTIVE:~I. To evaluate the efficacy of the combination of poziotinib and ramucirumab as measured by progression free survival.~SECONDARY OBJECTIVES:~I. To estimate the objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for the combination of poziotinib and ramucirumab.~II. To estimate the disease control rate (complete response + partial response + stable disease), overall survival, and duration of response of the study combination.~III. To assess the safety and the toxicity of the study combination.~EXPLORATORY OBJECTIVE:~I. To assess molecular markers associated with resistance and response to poziotinib and ramucirumab.~OUTLINE:~Patients receive poziotinib hydrochloride orally (PO) twice daily (BID) on day 1 and ramucirumab intravenously (IV) over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed at 30 days, then every 6 months thereafter.
This phase II trial tests whether poziotinib and ramucirumab work to shrink tumors in patients with EGFR Exon 20 gene mutant stage IV non-small cell lung cancer. Poziotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ramucirumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving poziotinib and ramucirumab may help to control the disease.