Background: Conventional chemotherapies possess intrinsic immune-regulatory properties. Some taxanes for instance, stimulate antigen presentation and impair regulatory T-cells while leaving effector T cells intact. Combining chemotherapies with immune checkpoint inhibitor at carefully designed dosing regimens may increase tumor cell susceptibility to immune-mediated death and thus enhance therapeutic efficacy. We describe the safety and updated efficacy of ABI and ipi in patients with metastatic melanoma. Methods: In this open-label, single center, phase II trial, ABI was administered to treatment naïve metastatic patients at 150mg/m² on days 1,8 and 15 every 4 weeks and ipi at 3mg/kg on day 1 every 3 weeks limited to 4 cycles until disease progression or unacceptable toxicity. Endpoints included ORR, OS and safety. Results: 18 of 21 enrollees between 6/2013 and 6/2015 with Stage IV melanoma (M1c: 56%, M1b: 33%, M1a: 11%) were included in the analysis. The median age was 57 years old (33-69) and 67% were men. 44% harbored BRAF mutations. Median duration of treatment was 9 weeks (5 to 17). Median follow-up time for OS analysis was 22.5 months (2 to 52 months). 12 and 24 month OS were 77.8% and 60.6% respectively with median not yet reached. The ORR by by irRECIST was 27.8%. Grade 3 adverse events were reported in 50% of patients, the most common being neutropenia. 17% of patients had grade 3 immune-related adverse events, the most common being hypophysitis and colitis. Immune analysis showed absolute lymphocyte count was significantly elevated post treatment compared with pre-treatment (p = 0.024). In addition, deep immune analysis of peripheral blood samples and tumor tissue including nanostring, gene expression and TCR sequencing will be assessed and reported. Conclusions: The combination of ipi and ABI in this small study demonstrates acceptable safety, tolerability and clinical activity. ABI may contribute to tumor cytoreduction and enhance antitumor clinical response of ipi without impactful immunosuppression. This data together with further immune analysis may provide rationale to design prospective chemo-immunotherapy regimens and treatments for metastatic melanoma and other solid tumors. Clinical trial information: NCT01827111