SAINT: A Phase I/Expanded Phase II Study Using Safe Amounts of Ipilimumab, Nivolumab and Trabectedin as First-Line Treatment of Advanced Soft Tissue Sarcoma

SIMPLE SUMMARY: The SAINT study is an early-stage clinical trial based on the hypothesis that immunotherapy is more effective when given earlier in the course of the disease in patients with advanced soft tissue sarcoma. It consists of two parts. Phase I aims to determine the maximum acceptable dose of a cancer drug known as trabectedin when combined with two immunotherapy drugs, ipilimumab and nivolumab, in previously treated patients with soft tissue sarcoma. Phase II of the study aims to determine if the combination of ipilimumab, nivolumab and trabectedin improves tumor control and survival of previously untreated patients with advanced soft tissue sarcoma. ABSTRACT: Background: This Phase 1/2 study is based on the hypothesis that immune checkpoint inhibitors are more effective when given earlier in the course of the disease for advanced soft tissue sarcoma. Methods: Phase I endpoints—maximum tolerated dose in previously treated patients; Phase II endpoints—best response, progression free survival and overall survival and incidence of adverse events in previously untreated patients; Phase I treatments—escalating doses of trabectedin (1.0, 1.2, 1.5 mg/m(2)) as continuous intravenous infusion over 24 h every 3 weeks, 1 mg/kg of ipilimumab given intravenously every 12 weeks, and 3 mg/kg of nivolumab given intravenously every 2 weeks; Phase II treatments—maximum tolerated dose of trabectedin and defined doses of ipilimumab and nivolumab. Results: Phase I (n = 9)—the maximum tolerated dose of trabectedin was 1.2 mg/m(2); Phase II (n = 79)—6 complete responses, 14 partial responses, 49 stable disease, 25.3% best response rate, 87.3% disease control rate; median progression-free survival, 6.7 months (CI 95%: 4.4–7.9), median overall survival, 24.6 months (CI 95%: 17.0–.); Grade 3/4 therapy-related adverse events (n = 92)—increased ALT (25%), fatigue (8.7%), increased AST (8.7%), decreased neutrophil count (5.4%) and anemia (4.6%). Conclusion: SAINT is a safe and effective first-line treatment for advanced soft tissue sarcoma.