Background: Primary lung cancer is increasingly understood as a heterogeneous disease made up of genomically defined subtypes requiring distinct treatment strategies. We hypothesize young age at diagnosis ( < 40 years) is a clinical characteristic associated with an increased chance for a targetable genomic alteration. This ALCMI study will prospectively characterize the somatic and germline genomics of young lung cancer. Our goals are to identify a genomically enriched subtype of lung cancer, facilitate delivery of targeted therapy and lay groundwork for further studies of heritable and environmental lung cancer risk factors. Methods: Accrual opened 07/2014. Patients are eligible if they were diagnosed with bronchogenic lung cancer less than age 40. A study specific website allows for virtual consenting so patients can participate remotely from anywhere in the country or the world; and use social media to share our trial. We have an integrated data and biorepository (Open Medicine Institute) that allows for seamless communication and completion of study activities like remote consenting, storage and routing of blood and tumor specimens. We have defined 7 genomic alterations of interest based on the Lung Cancer Mutational Consortium (LCMC) (EGFR, KRAS, HER2, BRAF, ALK, ROS1, RET). On study subjects without a known genotype will undergo comprehensive genomic profiling with the FoundationOne test to ensure that all of these genes have been tested. Subjects with advanced adenocarcinoma who are wild-type for all 7 genes will receive additional genomic profiling using the FoundationOne Heme test with the goal of identifying novel oncogenic drivers. Additional investigational genomics will include blood for germline analysis. All on study genomic analysis is at no cost to the participant. We aim to demonstrate that the prevalence of targetable genomic alterations will be greater in our population compared to the LCMC and have powered our study to show an increase from 35% to 50%; and an improvement in use of targeted therapy from 22% to 40%. The trial is currently accruing (NCT02273336) https://www.openmednet.org/site/alcmi-goyl. (Supported by grants from The Bonnie J. Addario Lung Cancer Foundation, Peter Barker Foundation, Genentech and Schmidt Legacy Foundation.) Clinical trial information: NCT02273336