The Phase 3 SELECT-MDS-1 trial evaluating tamibarotene in combination with azacitidine for patients with newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) failed to meet its primary endpoint. The study, designed to assess whether the combination improved the complete response (CR) rate compared to azacitidine alone in patients with RARA gene overexpression, did not demonstrate a statistically significant difference.
Topline Results
The trial enrolled 190 patients, with 126 receiving tamibarotene plus azacitidine and 64 receiving placebo plus azacitidine. The CR rate in the tamibarotene arm was 23.8% (95% CI, 16.7%-32.2%), while the placebo arm showed a CR rate of 18.8% (95% CI, 10.1%-30.5%). The difference between the arms did not reach statistical significance (P = 0.2084).
Safety and Tolerability
According to Syros Pharmaceuticals, the combination of tamibarotene and azacitidine was generally well-tolerated in the safety analysis of all 245 enrolled patients, with an adverse event profile consistent with prior studies.
Company Statement and Future Plans
"We are deeply disappointed by this outcome, particularly for the HR-MDS patients who are seeking a new treatment option for this challenging disease," said Conley Chee, chief executive officer of Syros. The company intends to halt the study, conduct a thorough review of the clinical data, and assess the next steps. Syros also acknowledged that the trial's failure constitutes an event of default under its secured loan agreement with Oxford Finance LLC.
SELECT-MDS-1 Trial Design
The SELECT-MDS-1 trial was a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of tamibarotene in combination with azacitidine versus placebo plus azacitidine in HR-MDS patients with RARA overexpression. Patients aged 18 years or older with newly diagnosed MDS, as per World Health Organization classification, were eligible. Additional criteria included RARA overexpression, high- or intermediate-risk disease per the Revised International Prognostic Scoring System for MDS, a bone marrow blast count of 5% or more, and an ECOG performance status of 0, 1, or 2.
Patients were randomized in a 2:1 ratio to receive either tamibarotene plus azacitidine or placebo plus azacitidine. The primary endpoint was the CR rate in the first 190 patients. Secondary endpoints included overall response rate, event-free survival, overall survival, transfusion independence, duration of response, duration of CR, time to response, time to CR, and safety.
