Background: Advanced soft tissue sarcoma is most often associated with a fatal outcome. This report is an update on the results of the SOC-1702 Phase 2 study for previously untreated STS. Methods: Objectives, Primary: Evaluate best response rate by RECIST v1.1; Secondary: Assess progression-free survival (PFS) at 6 months and overall survival. Patients and Methods: Eligible patients for this Phase 2 study are males or females ≥ 18 years of age with locally advanced unresectable or metastatic soft tissue sarcoma, previously untreated, with measurable disease by RECIST v1.1. Treatment protocol: (I) 1 mg/kg i.v. q 12 wks, (N) 3 mg/kg i.v. q 2 wks, (T) 1.2 mg/m2 CIV q 3 wks. Results: Efficacy: Ninety-one patients were evaluated for efficacy. These subjects completed at least two treatment cycles and had at least one follow-up CT scan. The best responses were 9CR, 14PR, 54SD and 14PD with 25% ORR, 85% DCR. PFS rate at 6 months was 56%; Median PFS was 7.4 (95% CI: 5.6-9.2) months; Median OS was 32.0 (95% CI: 19.8-44.2) months. The best responders (CR and PR) were patients with LMS, UPS, LPS, synovial sarcoma, myxofibrosarcoma, endometrial stromal sarcoma, clear cell sarcoma, DSRCT, and chondrosarcoma. Notably, out of the 91 patients who participated in the study between 2017 and 2022, 23 (25%) patients are still alive as of January 1, 2024, the data cut-off date. Safety: Grade 3/4 TRAEs related to Trabectedin include both hematologic and non-hematologic toxicities: fatigue, nausea, vomiting, fever, exhaustion, dehydration, asthenia, cellulitis of port, anemia, neutropenia, thrombocytopenia, transaminitis, elevated CK. There were no hematologic toxicities related to Nivolumab or Ipilimumab. Grade 3/4 TRAEs include decreased TSH, increased T4, increased TSH, transaminitis, hyponatremia, dehydration, pruritus, and psoriasis. Conclusions: Taken together we have confirmed that (1) Trabectedin in combination with Ipilimumab and Nivolumab is a safe and effective regimen for previously untreated advanced STS, and (2) Randomized studies are needed to confirm whether this regimen is superior to standard first line therapy for advanced soft tissue sarcoma. Clinical trial information: NCT03138161.