Background: There have been no advances in the systemic treatment of resected lung cancers in the last decade. This is in contrast to advanced disease where molecularly targeted therapies for patients with oncogene-driven tumors have replaced and/or delayed chemotherapy and where immunotherapy drugs that target the programmed death receptor pathway (PD-1 or PD-L1) are now utilized in first and second line. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is a National Cancer Institute (NCI) sponsored National Clinical Trials Network (NCTN) initiative to address the role of genomic testing and personalized therapies in the adjuvant treatment of non-small cell lung cancers. EA5142 is the newest of the ALCHEMIST studies, investigating adjuvant nivolumab in patients not eligible for the EGFR or ALK directed trials. Methods: ALCHEMIST is a clinical trial platform that consists of integrated protocols: ALCHEMIST Screening (A151216; NCT02194738), ALCHEMIST-EGFR (A081105; NCT02193282), ALCHEMIST-ALK (E4512; NCT02201992), and ALCHEMIST-nivo (EA5142; NCT02595944). In ALCHEMIST-Screening, up to 8,000 patients with pathologically confirmed stage IB (≥ 4 cm)-IIIA NSCLC will be enrolled either before or after surgical resection. Tumors that are non-squamous histology will be centrally genotyped for EGFR mutations and ALK rearrangements. Patients with EGFR or ALK-positive tumors are offered enrollment in trials evaluating adjuvant erlotinib or crizotinib, respectively. In the ~80% of patients enrolled with tumors that have wildtype EGFR and ALK or those with squamous histology central testing will be performed for PD-L1 utilizing immunohistochemistry (DAKO 28-8). Adjuvant therapy is allowed but not required. Patients are randomized to nivolumab 240 mg IV over 3 minutes every 2 weeks for up to 1 year versus standard of care observation, stratified by stage, histology, prior adjuvant treatment, and PD-L1 status ( > / = 1% or < 1%). ANVIL has enrolled 52 of 714 planned patients to detect co-primary endpoints of a 30% improvement in overall survival and/or a 33% reduction in disease free survival favoring nivolumab. EA5142 is currently open at over 400 centers nationwide. Clinical trial information: NCT02595944