On April 28, 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 multiple myeloma patient with TTI-622 (SIRPα-IgG4 Fc), an investigational checkpoint inhibitor of the innate immune system, in combination with the proteasome inhibitor carfilzomib and dexamethasone (Press release, Trillium Therapeutics, APR 28, 2021, View Source [SID1234578615]).
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TTI-622 is a fusion protein that is designed to block the inhibitory activity of CD47, a molecule that is overexpressed by a wide variety of tumors. CD47 binds to SIRPα on macrophages and delivers a "don’t eat me" signal that inhibits the ability of macrophages to engulf and destroy cancer cells. Preclinical studies have shown that TTI-622 exhibits anti-myeloma activity as a monotherapy that is enhanced when combined with proteasome inhibitors.
"With the dosing of this patient we have begun an exciting new phase of development for TTI-622," commented Dr. Ingmar Bruns, Trillium’s Chief Medical Officer. "This is the first patient to receive TTI-622 in combination with another anti-cancer agent, and we are eager to build upon the monotherapy activity that we have observed in multiple hematologic cancers. More broadly, this marks the start of a comprehensive Phase 1b/2 program that will evaluate TTI-622 with various combination agents in five indications and six patient settings."
The combination of TTI-622 and carfilzomib plus dexamethasone is being assessed as part of the ongoing, open-label Phase 1a/1b study (NCT03530683). Approximately 30 relapsed/refractory multiple myeloma patients who have received at least 3 prior lines of therapy which must include a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody will be enrolled. The primary endpoints are safety and overall response rate.
"Despite the development of new therapeutics and combinations, there remains a significant unmet medical need for myeloma patients who relapse after earlier lines of therapy," added Dr. Bruns. "CD47 is overexpressed in multiple myeloma and the overexpression is further increased in relapsed multiple myeloma. We therefore believe that the combination of TTI-622 and carfilzomib plus dexamethasone has strong potential to address the unmet need and have a significant impact on the myeloma treatment landscape, if approved."