Update on SAINT: A phase II study using trabectedin (T) in combination with ipilimumab (I) and nivolumab (N) in previously treated soft tissue sarcoma

BackgroundAdvanced soft tissue sarcoma is most often associated with a fatal outcome. This report provides an update on SAINT: A Phase I/Expanded Phase II Study Using Safe Amounts of Ipilimumab, Nivolumab and Trabectedin as First-Line Treatment of Advanced STS.MethodsPrimary: 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 II 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.ResultsNinety-seven 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 6CR, 17PR, 57SD and 17PD with 24.7% ORR, 82.5% DCR. PFS rate at 6 months was 55%; Median PFS was 7.3 (95% CI: 5.247-9.353) months; Median OS was 32.0 (95% CI: 20.575- 43.425) months. The best responders (CR and PR) were patients with LMS, UPS, LPS, synovial, MFS, endometrial stromal, clear cell, DSRCT, spindle cell, and chondrosarcoma. Notably, out of the 97 patients who participated in the study between 2017 and 2024, 16 (17%) patients are still alive as of April 30, 2024, the data cut-off date. 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.ConclusionsTaken 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 identificationNCT03138161.Legal entity responsible for the studySarcoma Oncology Research Center, LLC.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.