Background: Although osimertinib has recently become an option for adjuvant therapy in many countries, biomarkers predicting the efficacy of adjuvant EGFR-TKI and the risk of postoperative recurrence in completely resected NSCLC harboring EGFR mutations have not been fully investigated. Methods: This IMPACT-TR study is an exploratory biomarker study for completely resected, EGFR-mutated NSCLC patients who received gefitinib or cisplatin plus vinorelbine (cis/vin) in a phase III IMPACT study (Trial registration number: UMIN000044738. Funding: AstraZeneca K.K.). Surgically resected lung cancer tissue specimens were analyzed for co-existing somatic mutations and tumor mutation burden (TMB) determined by Oncomine Tumor Mutation Load, and these data were matched with disease free survival (DFS) and overall survival (OS) data. Results: Of the 234 patients in the IMPACT study, 211 patients were enrolled, and 202 patients in the Per Protocol Set were analyzed. The most frequent co-existing somatic mutation was TP53 (58.4%), followed by CSMD3 (11.8%), NOTCH1 (9.9%) and SYNE1 (9.9%). The median TMB was 6.67 mutations/Mb, and only 15.2% had ≥10 mutations/Mb. EGFR mutation subtypes, TP53 co-mutation and TMB were not associated with DFS or OS in either the gefitinib or cis/vin groups. In the gefitinib group, patients with NOTCH1 mutation had significantly shorter OS (hazard ratio [HR] 4.18, 95%CI 1.65-10.61, p=0.003) and tended to have shorter DFS (HR 1.44, 95%CI 0.62-3.37, p=0.399) than those without NOTCH1 mutation. In the cis/vin group, patients with CREBBP mutation had significantly shorter DFS (HR 2.70, 95%CI 1.05-6.97, p=0.040) and tended to have shorter OS (HR 3.05, 95%CI 0.90-10.37, p=0.074) than those without CREBBP mutation. Conclusions: This study suggested that NOTCH1 mutation may be a biomarker to predict poor response to adjuvant gefitinib and CREBBP mutation to predict poor response to cis/vin in patients with completely resected, EGFR-mutated NSCLC. Clinical trial information: UMIN000044738.