Syros Pharmaceuticals experienced a significant setback as its Phase III SELECT-MDS-1 trial evaluating tamibarotene in combination with azacitidine for newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) failed to meet its primary endpoint. The study, which focused on patients with RARA gene overexpression, did not demonstrate a statistically significant improvement in complete response rate compared to placebo.
The placebo-controlled trial enrolled 190 patients. The complete response rate was 23.8% in the tamibarotene plus azacitidine arm and 18.8% in the placebo plus azacitidine arm. While the company reported that the therapy was well-tolerated, the lack of efficacy has led to the discontinuation of the study.
Conley Chee, CEO of Syros, stated that the company plans to thoroughly review the results and evaluate the next steps. The failure of the SELECT-MDS-1 trial also triggers a default event under Syros' secured loan facility with Oxford Finance, obtained in 2022.
This news comes shortly after Syros announced that a Phase II trial of tamibarotene in acute myeloid leukemia (AML) was unlikely to meet its primary endpoint, further impacting the company's stock value. The futility analysis of the AML trial indicated a low probability of success based on the data from the first 40 randomized patients.
Tamibarotene is a selective agonist of retinoic acid receptor alpha/beta, potentially binding to retinoid X receptors (RXR). These receptors play a role in regulating transcription of signaling pathways involved in cancer hallmarks, including inflammation, immune responses, and tumor microenvironment modulation.
The myelodysplastic syndromes (MDS) are a group of diverse blood cancers in which the bone marrow does not produce enough healthy blood cells. HR-MDS carries a particularly poor prognosis, with many patients progressing to acute myeloid leukemia. Current treatment options for HR-MDS include azacitidine and decitabine, hypomethylating agents that can improve survival and quality of life. Allogeneic stem cell transplant can be curative, but is only an option for a minority of patients. There remains a significant unmet need for more effective therapies for HR-MDS.
