Syros Pharmaceuticals is facing significant setbacks after its Phase III SELECT-MDS-1 trial of tamibarotene in combination with azacitidine failed to meet its primary endpoint. The trial, designed to evaluate the efficacy of the combination therapy in newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) patients with RARA gene overexpression, showed similar complete response rates in both the treatment and placebo groups.
The placebo-controlled Phase III study enrolled 190 patients. The complete response rate, the study’s primary endpoint, was 23.8% in the tamibarotene plus azacitidine arm and 18.8% in the placebo plus azacitidine arm. Despite the failure to meet the primary endpoint, Syros reported that the therapy was well-tolerated.
According to Syros CEO Conley Chee, the company plans to discontinue the study and thoroughly review the results to determine the next steps. This news comes shortly after a futility analysis indicated a low probability of success for a Phase II trial evaluating tamibarotene in acute myeloid leukemia (AML).
Tamibarotene is a selective agonist of retinoic acid receptor alpha/beta, with potential binding to retinoid X receptors (RXR). These receptors play a role in regulating transcription of signaling pathways that influence cancer hallmarks by controlling inflammation, immune responses and modulating the tumor microenvironment.
The failure of the SELECT-MDS-1 trial also constitutes a default event under Syros' secured loan facility with Oxford Finance, obtained in 2022. The company's stock price has declined sharply following the announcement.
