On June 29, 2021 Trillium Therapeutics Inc. (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that it has dosed the first patient with TTI-621 (SIRPα-IgG1 Fc), an investigational checkpoint inhibitor of the innate immune system, in combination with doxorubicin in a Phase 1b/2 study in leiomyosarcoma (LMS) (Press release, Trillium Therapeutics, JUN 29, 2021, View Source [SID1234584474]).
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TTI-621 binds CD47, an innate immune checkpoint that binds SIRPα and delivers a "don’t eat me" signal to suppress macrophage phagocytosis. Overexpression of CD47 can allow tumor cells to escape immune surveillance. TTI-621 is a fusion protein consisting of the CD47 binding domain of SIRPα linked to the Fc region of human IgG1. It is designed to enhance phagocytosis and tumor cell destruction by blocking the CD47-SIRPα interaction and delivering an activating ("eat me") signal to macrophages. The IgG1 backbone can also activate NK cell-mediated anti-tumor activity. Published preclinical studies suggest that anti-CD47 agents may exhibit anti-tumor activity against LMS cells.
"The dosing of this patient marks the beginning of the first Phase 1b/2 solid tumor clinical trial for Trillium," commented Dr. Ingmar Bruns, Trillium’s Chief Medical Officer. "We’re committed to exploring solid tumors and build upon our potentially best-in-class initial hematologic malignancy datasets."
For newly diagnosed LMS patients, doxorubicin is considered part of standard of care. In this open-label Phase 1b/2 study, Trillium is adding TTI-621 to frontline doxorubicin and enrolling approximately 60 newly diagnosed LMS patients. The primary endpoints are safety and overall response rate.
"Metastisized LMS, the most common form of soft tissue sarcoma, is a serious disease with significant unmet need. We believe that the combination of TTI-621 and doxorubicin has the potential to provide benefit for these patients where few therapeutic options exist," added Dr. Bruns.