Background: BMS-986253 is a novel fully human monoclonal antibody that binds to and inhibits IL-8, a chemokine that promotes immune escape and tumor progression. High serum IL-8 levels correlate with poor prognosis in various tumors (Sanmamed et al. Clin Cancer Res. 2014). IL-8 stimulates recruitment of myeloid-derived suppressor cells (MDSCs) and promotes epithelial-mesenchymal transition (EMT) in tumors conferring resistance to immune-mediated killing (David et al. Vaccines 2016). We have previously shown the ability of BMS-986253 to reduce mesenchymal features in cancer cells leading to enhanced susceptibility to NK and T cell-mediated lysis, and to decrease the frequency of granulocytic MDSCs in xenograft models. Decreases in serum IL-8 were also associated with response to anti–PD1 therapy in a small cohort of patients with melanoma and NSCLC (Sanmamed et al. Ann Oncol. 2017). Methods: Patients with metastatic or unresectable locally advanced malignant solid tumors were treated with BMS-986253 monotherapy at 4, 8, 16, or 32 mg/kg IV Q2W in a phase I, open-label, 3+3 dose-escalation study. The primary objective was to determine the safety and tolerability and establish the maximum tolerated dose (MTD). Pharmacokinetics and changes in serum cytokine levels including IL-8 were also evaluated. Results: Amongst 15 patients, no serious treatment-related adverse events (TRAEs) were observed and MTD was not identified through 32mg/kg. TRAEs occurred in 5 pts (33%), and all were Grade 1 except for Grade 2 fatigue, hypophosphatemia and hypersomnia in two patients receiving 32mg/kg. Eleven pts (73%) achieved stable disease (per RECIST v1.1) and 4 patients had progressive disease (27%). The progression free survival rate at 24 weeks for all patients was 73% with two-sided 95% CI [44%, 89%]. Reductions in serum IL-8 levels were observed at all dose levels. Conclusions: BMS-986253 monotherapy is well tolerated and associated with decreases in serum IL-8 across all doses tested. These data have informed combining this drug with Nivolumab and potentially other agents to evaluate the potential for synergetic activity in selected patient populations. Clinical trial information: NCT02536469