This phase II trial studies how well ramucirumab and pembrolizumab work in treating EGFR mutant non-small cell lung cancer that has come back (recurrent) or spread to other places in the body (metastatic). Ramucirumab may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ramucirumab and pembrolizumab may work better in treating EGFR mutant non-small cell lung cancer compared to pembrolizumab alone.
Name: Pembrolizumab
Name: Ramucirumab
Description: Response rate will be evaluated with computed tomography (CT) scans every 2 cycles and tumor measurements using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Immune RECIST (iRECIST) will also be assessed.
Measure: Overall response rate Time: Up to 2 yearsDescription: Common Terminology Criteria for Adverse Events version 4.0 will be used for adverse event grading. Attributions of causality will be assessed by the primary treating physician. Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized by descriptive statistics for each of the disease cohorts.
Measure: Incidence of adverse events Time: Up to 2 yearsDescription: Clinical benefit rate will be evaluated with CT scans every 2 cycles and tumor measurements using RECIST 1.1 criteria. iRECIST will also be assessed.
Measure: Clinical benefit rate (complete response + partial response + stable disease) Time: Up to 2 yearsDescription: Kaplan-Meier curves will be calculated to estimate progression-free survival.
Measure: Progression-free survival Time: From the date of study registration to the date of progressive disease, assessed up to 2 yearsDescription: Kaplan-Meier curves will be calculated to estimate overall survival.
Measure: Overall survival Time: From the date of study registration to the date of death, assessed up to 2 yearsDescription: Measured by immunohistochemistry, including tumor infiltrating lymphocytes and T cell receptor (TCR) immunosequencing (immunoSEQ) and relationship to clinical outcomes, including response rate. TCR immunoSEQ data will be summarized for each patient for T-cell clonality difference, descriptive statistics and confidence interval will be obtained across patients.
Measure: Tumor immunoprofile Time: BaselineDescription: Measured using 10-color 65 marker multiplex Clinical Laboratory Improvement Act-certified IMMUNOME flow cytometry profile on peripheral blood samples. For immune cell subpopulation data by flow cytometry, will identify differences between the paired peripheral blood mononuclear cell samples from the same patients.
Measure: Circulating immune cell profiles in response to treatment and in relation to clinical response Time: Up to 2 yearsDescription: Will evaluate correlation with clinical response. A bivariate plot will be used to describe the relationship between response rate and peak VEGF via enzyme-linked immunosorbent assay over time.
Measure: Change in circulating VEGF levels Time: Baseline up to 2 yearsAllocation: N/A
Single Group Assignment
There is one SNP
Patients who develop progressive disease after erlotinib, gefitinib, afatinib, or dacomitinib must either receive osimertintib (T790M positive) or be T790M negative. --- T790M ---
Patients who develop progressive disease after erlotinib, gefitinib, afatinib, or dacomitinib must either receive osimertintib (T790M positive) or be T790M negative. --- T790M --- --- T790M ---