Background: Metronomic dosing of gemcitabine, doxorubicin and docetaxel causes less severe side effects than standard chemotherapy for advanced sarcoma. The addition of nivolumab to this regimen has potential to have synergistic effects and improve treatment outcomes. Methods: Primary objective: To assess progression-free survival (PFS); Secondary objectives: (1) To evaluate best overall response during treatment period confirmed in a 6-week follow-up, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 12 months, and (4) Incidence of treatment-related adverse events (TRAEs). Inclusion criteria: Previously treated male and female subjects, ≥ 18 years of age, pathologically confirmed diagnosis of locally advanced, unresectable, or metastatic sarcoma, measurable disease by RECIST v1.1, and acceptable hematologic and organ functions. Exclusion Criteria: History of autoimmune disorder. Treatment schedule: Metronomic doses of gemcitabine (600 mg/m2 max:1000 mg), doxorubicin (18 mg/m2; max: 32 mg), docetaxel (25 mg/m2; max:42 mg) on Day 1 and Day 8, and nivolumab (240 mg) on Day 1 only. Repeat treatment cycles are continued every three weeks if the toxicity grade is ≤1. Results: This report on the modified intent-to-treat population (n=59). This population completed at least one treatment cycle and had a follow-up CT or MRI scan at week 6. Best Overall Response = 8 PR, 44 SD, 7 PD. The disease control rate ( CR+PR+SD) was 88.1%. Median PFS was 5.1 (95% CI: 2.837-7.363) months; 6 month PFS rate 52.5%. Median OS, 15.3 (95% CI: 5.48-25.12) months, with 6-month OS 88%. Safety analysis: Grade 3/4 TRAEs include fatigue (n=18), nausea (n=13), neutropenia (n=10), thrombocytopenia (n=9), anemia (n=9), diarrhea (n=1). There were no unexpected adverse events. Conclusions: Taken together, the data suggests that nivolumab in combination with metronomic doses of gemcitabine, doxorubicin and docetaxel (1) may have synergistic activity, and (2) by indirect comparison, may be as effective as standard first line therapy for advanced sarcoma with manageable toxicity. Clinical trial information: NCT04535713.