A phase 2 randomized study of osimertinib versus osimertinib plus chemotherapy for patients with metastatic EGFR-mutant lung cancers that have detectable EGFR mutant cfDNA in plasma after initiation of osimertinib treatment

This study will compare the effectiveness of osimertinib alone to the combination of osimertinib and chemotherapy (carboplatin and pemetrexed) in people with metastatic lung cancer that has a change (mutation) in the gene for the epidermal growth factor receptor (EGFR). Osimertinib alone is the usual treatment for metastatic EGFR-mutant lung cancer. This study will be adding chemotherapy to osimertinib, which could possibly add to the anticancer effects of the usual treatment and may help stop cancer from growing or spreading. Osimertinib binds to the EGFR protein and blocks its activity, which slows the tumor growth. Another purpose of this study is to compare the safety of the study groups' approaches (osimertinib alone versus osimertinib with chemotherapy) and see which approach causes fewer and more mild side effects. The two study groups for this study are Arm A which will receive osimertinib alone and Arm B which will receive carboplatin, pemetrexed, and osimertinib. Participants will be randomized by a computer and participants will have a 1 in 2 (50%) chance of being randomized to either of the treatment group. Randomized means that the participants in this study will be assigned by chance to separate groups that are given different treatments or other interventions. Neither the researcher nor the participant chooses which treatment or intervention the participant will receive.

Are you Eligible? (Inclusion Criteria)

• You are at least 18 years old -You have biopsy proven metastatic non-small cell lung cancer, confirmed at enrolling institution -You have either not started a prior epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy, or may have started osimertinib within 1 week of confirming eligibility and enrollment criteria as approved by the study doctor, with no prior chemotherapy for treatment of disease that has spread to other parts of your body -You are able to swallow oral medications