9500 Background: Dabrafenib plus trametinib, a standard-of care adjuvant treatment for patients with BRAF-mutated AJCC-stage III melanoma, has significantly improved the primary endpoint, relapse-free survival (RFS). Further to published interim assessments, we present updated and final results for RFS, distant-metastasis-free survival (DMFS) and overall survival (OS). Methods: In the COMBI-AD phase 3 study, patients received dabrafenib (150 mg BD) plus trametinib (2 mg OD; n=438) or matching placebos (n=432). Treatment continued for up to 12 months or until disease relapse, unacceptable toxicity, withdrawal of consent, or death. OS, RFS, and DMFS were summarized using Kaplan–Meier estimates. OS was compared between study arms using stratified log-rank test. Hazard ratio (HR) was calculated using Pike estimator. Safety data were summarized descriptively. Results: At final analysis, median duration of follow up was 100.0 months in the treatment arm and 82.5 months in the placebo arm. Median OS was not attained in the two arms (HR: 0.80; 95% CI: 0.62, 1.01; P=0.063). Consistent OS benefits were seen across most prespecified subgroups including patients with BRAFV600E mutation (n=397; HR: 0.75; 95% CI: 0.58, 0.96). Estimated RFS (HR: 0.52; 95% CI: 0.43, 0.63) and DMFS (HR: 0.56; 95% CI: 0.44, 0.71) favored the dabrafenib plus trametinib arm. In both arms, patients received salvage immunotherapies (29% each) and targeted therapy (21% vs. 37% for treatment and placebo arms, respectively). Safety profile was consistent with previous reports. Conclusions: COMBI-AD presents the longest follow-up data (over 10 years) in adjuvant treatment of stage III melanoma in the modern era. OS was improved with dabrafenib plus trametinib over placebo for adjuvant treatment of stage III melanoma with a 20% risk reduction for death. However, this difference was not statistically significant. Consistent with published results at 3 and 5 years, RFS and DMFS were more favorable in the treatment vs. placebo arm. Clinical trial information: NCT01682083 . [Table: see text]