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. 2023 Jan 31;15(3):906.
doi: 10.3390/cancers15030906.

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

Erlinda Maria Gordon  1   2 , Sant P Chawla  1 , Walter Andree Tellez  1 , Elan Younesi  1 , Sonu Thomas  1 , Victoria S Chua-Alcala  1 , Hripsime Chomoyan  1 , Chrysler Valencia  1 , Don Arlen Brigham  2 , Ania Moradkhani  1 , Doris Quon  1 , Amornchit Srikureja  1 , Steven G Wong  1 , William Tseng  3 , Noah Federman  4
Affiliations

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

Erlinda Maria Gordon et al. Cancers (Basel). .

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/m2) 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/m2; 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.

Keywords: alkylating agent; chemotherapy; immune checkpoint inhibitor; immunotherapy; ipilimumab; nivolumab and trabectedin; soft tissue sarcoma.

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Conflict of interest statement

The authors E.M.G., S.P.C., W.A.T., E.Y., S.T., V.S.C.-A., H.C., C.V., D.A.B., A.M., S.G.W., D.Q., A.S., N.F., W.T. have no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Graphic illustration of the mechanism of action of Ipilimumab, Nivolumab and Trabectedin in the tumor microenvironment. Ipilimumab (I) blocks the CTLA 4 receptor and nivolumab (N) blocks the PD-1 receptor on T cells which then block the PD1- PD-L1 interaction on tumor cells. Trabectedin (T) not only kills cancer cells but depletes the tumor microenvironment of growth promoting or M2 macrophages. The combined effect of these three drugs is sustained T cell activation, resulting in tumor lysis, inhibition of tumor growth or tumor eradication.
Figure 2
Figure 2
Kaplan–Meier graphs of overall survival and progression free survival for the mITT patients in Phase II of the study. (A,B) Percent survival is plotted on the vertical axis as a function of time from treatment initiation (months) plotted on the horizontal axis.
See this image and copyright information in PMC

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