Background: Most melanoma pts are diagnosed with earlier-stage, surgically resectable disease. Although there are approved adjuvant immunotherapy (IT) and targeted therapy (TT) options available, neoadjuvant systemic treatment (NST) has demonstrated improved outcomes based on pathologic complete response (pCR). We previously reported outcomes from a randomized trial comparing neo +adj DT vs upfront surgery followed by adj DT in pts with surgically resectable stage III/IV BRAF mutated melanoma. After enrolling 21 pts, the randomized study was closed by the Data Safety Monitoring Board due to rapid disease progression in pts randomized to upfront surgery. The trial continued as a single-arm study to evaluate neo + adj DT. With a median follow up of 35 mos (range 6-97 mos), we report the updated outcomes for the pts evaluable for the primary endpoint. Methods: We conducted a single-center, phase II clinical trial (NCT02231775) evaluating neo + adj DT in pts with surgically resectable, RECIST measurable clinical stg III or oligometastatic stg IV BRAF V600E/K mutated melanoma. Study objectives included determination of pCR and survival outcomes based on INMC path response. Pts received oral D 150mg BID and T 2mg daily for 8 wks prior to surgery and 44 wks of adjuvant DT starting 1wk post-surgery. Imaging was performed prior to surgery to determine the RECIST 1.1 objective response rate (ORR) and then every 12 wks to monitor for recurrence. Results: Of the 51 pts who received neo DT, 49 were considered evaluable for the primary endpoint unrelated to progression prior to surgery. Median age was 56 (IQR 45-66). 10 pts received prior adj IT. All but 1 pt underwent surgery on time with delay due to treatment related toxicity. The radiographic ORR was 78%, including 6 (12%) CR. 17 (35%) pts achieved a pCR, 7 (14%) near pCR, 12 (24%) partial path response, and 13 (27%) path non-response. 47 (96%) pts initiated adj treatment; 23 (47%) completed all planned adj treatment, 7 (14%) discontinued adj treatment due to recurrence and 12 (24%) due to toxicity. Median RFS for all pts was 17.6 mos (95% CI: 14,40.1) and was improved for pts with pCR versus non-pCR [median Not Reached (NR) vs 11.3 mos; p = 0.0002]. Median distant metastasis free survival (DMFS) for all pts was 48.9 mos (95% CI: 24.1, NA) and was also improved for pCR pts (median NR vs 17.5 mos; p = 0.0004). Median OS was not reached for all pts and was improved in pCR pts (p = 0.03). No new safety signals were seen. Conclusions: Neo + adj DT is feasible and safe in pts with surgically resectable BRAF mutated melanoma. With a median follow-up of 35 mos, median RFS, DMFS, and OS have not been reached for pts with a pCR after neo DT, and are all significantly prolonged compared to non-pCR pts. These results demonstrate durable benefit for neo + adj DT in this high-risk pt population that achieve a pCR. Clinical trial information: NCT02231775.