(P 137) SAINT: FIVE YEAR RESULTS OF A PHASE 2 TRIAL USING IPILIMUMAB (I), NIVOLUMAB (N) AND TRABECTEDIN (T) FOR PREVIOUSLY UNTREATED ADVANCED SOFT TISSUE SARCOMA [NCT03138161]

Objective: Background: Advanced soft tissue sarcoma (STS) has a median survival of 8-13 months. Hypothesis: To improve survival, immune checkpoint inhibitors that promote sustained T cell activation would be most effective when given earlier in the course of disease when cancer cells are most immunogenic.
Objectives: Primary: Evaluate best response rate by RECIST v1.1; Secondary: Assess progression-free survival (PFS) at 6 months and overall survival; Exploratory: Correlate response and PD-L1 expression and oncogenic drivers in archived tumors; correlate effect of dexamethasone on absolute lymphocyte count.

Methods: 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: Seventy-nine of 92 subjects were evaluable for efficacy analysis. These subjects completed at least one treatment cycle and had a follow-up CT scan. The median time to follow up was 18.1 months. The best responses were 9CR (3 surgical CR), 12PR, 48SD and 10PD with 26.6% ORR, 87.3% DCR. Median PFS was 6.7 months, Median OS, 24.6 months; 6-month PFS Rate was 53.2% and 6-month OS Rate, 89.9%. Best responders (CR and PR) were patients with LMS, UPS, LPS, synovial sarcoma, myxofibrosarcoma, endometrial stromal sarcoma and clear cell sarcoma. Exploratory: There was no correlation between treatment outcome parameters and PD-L1 expression or other oncogenic drivers found in patients’ archived tumors. Dexamethasone administration given with Trabectedin every 3 weeks was not associated with a significant reduction in ALCs.
Safety: Grade 3/4 TRAEs related to Trabectedin include both hematologic and non-hematologic toxicities: fatigue, nausea, 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.

Conclusion: (1) The SAINT protocol may be equal or superior to Doxorubicin alone as first line therapy for advanced or metastatic soft tissue sarcoma by indirect comparison, and (2) The SAINT protocol may be safer than standard chemotherapy as first line therapy for advanced STS.