(P 123) COMPLETE RESPONSES WITH SAINT PROTOCOL: A PHASE 2 STUDY USING SAFE AMOUNTS OF IPILIMUMAB, NIVOLUMAB, AND TRABECTEDIN IN PREVIOUSLY UNTREATED PATIENTS WITH ADVANCED SOFT TISSUE SARCOMA (NCT03138161)

Objective: The timing of treatment initiation for advanced soft tissue sarcoma (STS) could impact tumor responses when using immune checkpoint inhibitors since sarcoma cells are more immunogenic at the onset of disease. Hypothesis: Immune checkpoint inhibitors may be more effective when given as first line therapy and may synergize with trabectedin, a marine derived alkaloid that depletes the tumor microenvironment of growth promoting macrophages.
Objectives: Primary: Evaluate best response by RECIST v1.1; Secondary: Assess progression-free survival (PFS) at 6 months and overall survival;

Methods: Eligible patients for this Phase 2 study are males or females ≥ 18 years of age with previously untreated locally advanced unresectable or metastatic STS with measurable disease by RECIST v1.1. Treatment protocol: Ipilimumab (I) 1 mg/kg i.v. q 12 weeks, Nivolumab (N) 3 mg/kg i.v. q 2 weeks, Trabectidin (T) 1.2 mg/m2 CIV q 3 weeks. Efficacy Analysis: BOR, PFS, OS. Safety Analysis: Incidence of Adverse Events.

Results: Ninety-two patients were enrolled, and 79 patients were evaluable for efficacy analysis. Remarkably, 12/79 (11.4.0%) patients achieved an improvement in tumor responses (PR or CR) with continued treatment from 2-7 treatment cycles. Of these patients, 9/12 (75%) achieved CR after 2-7 cycles, and 3/12 (25%) had a surgical CR after 2-3 cycles. All patients had either SD or PR after one treatment cycle at Week 6. The histologic subtypes include UPS (n=3), uterine LMS (n=2), dedifferentiated LPS (n=2), synovial sarcoma (n=2), clear cell sarcoma (n=1), myxofibrosarcoma (n=1) and spindle cell sarcoma (n=1). As shown in Table, PUPs who achieved PR and CR (n=12) had a median PFS of 7.2 months; median OS, 29.7mos; 6-month PFS rate, 83%; 6-month OS rate, 100%. Grade 3/4 TRAEs include fatigue (n=1), inc. AST (n=3), inc. ALT (n=5), inc. TSH (n=1), inc. CK (n=1), hyponatremia (n=1).

Conclusion: Taken together, these data indicate that (1) Complete and partial responses can be achieved by continued treatment with the SAINT protocol (I, N, T), 2) The SAINT protocol may be superior to standard first line therapy for certain advanced STS types, and 3) The SAINT protocol may be safer than standard first line therapy for advanced STS.

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