Background: There have been no advances in the systemic treatment of resected lung cancers in the last decade. In contrast, targeted therapies and immunotherapies have demonstrated benefit in advanced disease. Furthermore, adjuvant immunotherapy after concurrent chemoradiation in locally advanced non-small cell lung cancer (NSCLC) has demonstrated improvement in progression free survival. The role of adjuvant immunotherapy after surgery remains unknown. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is a National Cancer Institute sponsored National Clinical Trials Network initiative to address the role of genomic testing and personalized therapies in the adjuvant treatment of NSCLC. EA5142 is the arm of the ALCHEMIST 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; ANVIL). In ALCHEMIST-Screening, up to 8,000 patients with pathologically confirmed stage IB (≥ 4 cm)-IIIA NSCLC will be enrolled 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 by immunohistochemistry (DAKO 28-8). Adjuvant chemotherapy and/or radiotherapy is allowed but not required. Patients are randomized to nivolumab versus standard of care observation, stratified by stage, histology, prior adjuvant treatment, and PD-L1 status (≥1% or < 1%). ANVIL is active at over 600 US sites and is actively enrolling. The study statistical plan is to detect co-primary endpoints of a 30% improvement in overall survival and/or a 33% improvement in disease free survival favoring nivolumab. EA5142 design changes under review at CTEP will be presented. Clinical trial information: NCT02595944