SELECT-MDS-1 Trial of Tamibarotene Misses Primary End Point in MDS
The SELECT-MDS-1 trial showed no significant complete response rate improvement with tamibarotene plus azacitidine for high-risk myelodysplastic syndrome, leading to the trial being discontinued.
Red blood cells: © vipman4 - stock.adobe.com
In the phase 3 SELECT-MDS-1 trial (NCT04797780), the combination of tamibarotene (formerly SY-1425) and azacitidine did not reach the primary end point of improving the complete response (CR) rate over azacitidine alone in patients with newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) showing RARA gene overexpression.1
Among the initial 190 patients enrolled, the CR rate in the tamibarotene plus azacitidine arm (n = 126) was 23.8% (95% CI, 16.7%-32.2%) vs 18.8% (95% CI, 10.1%-30.5%) in the placebo plus azacitidine control arm (n = 64), with the difference not reaching statistical significance (P =.2084).
In a safety analysis of all enrolled patients (n = 245), the combination of tamibarotene and azacitidine (n = 160) was generally well-tolerated, with an adverse event profile that was consistent with earlier studies.
“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, in a press release. “We plan to stop the study, review the clinical data more thoroughly, and evaluate the next steps. We want to express our sincere appreciation for the patients, caregivers and healthcare professionals who took part in the SELECT-MDS-1 trial and to all the employees of Syros for their exceptional work on the tamibarotene program.”
Syros Pharmaceuticals, the developer of tamibarotene, reported that this result constitutes an event of default under its secured loan agreement with Oxford Finance LLC. Consequently, the trial will be discontinued.
Tamibarotene and the Phase 3 SELECT-MDS-1 Trial
Tamibarotene is an oral and selective RARα agonist specifically designed to target RARA-driven disease pathways.
The phase 3, randomized, double-blind, placebo-controlled SELECT-MDS-1 study sought to assess the efficacy and safety of the combination of tamibarotene and azacitidine vs placebo plus azacitidine in patients with HR-MDS with RARA overexpression.2
Enrollment was open to patients aged 18 years or older with newly diagnosed MDS per World Health Organization classification. Patients were also required to have RARA overexpression, as determined by an investigational blood test and very high–, high-, or intermediate-risk disease per Revised International Prognostic Scoring System for MDS classification. Further, measurable disease, a bone marrow blast count of 5% or more, and an ECOG performance status of 0, 1, or 2 were required.
Once patients were enrolled, they were randomly assigned in a 2:1 fashion to receive either tamibarotene in combination with azacitidine or placebo with azacitidine.
CR rate in the first 190 patients was the primary end point of the study, and secondary end points consisted of overall response rate, event-free survival, overall survival, transfusion independence, duration of response, duration of CR, time to response, time to CR, and safety.
REFERENCES:
Syros announces topline data from SELECT-MDS-1 phase 3 trial of tamibarotene in higher-risk myelodysplastic syndrome with RARA gene overexpression. News Release. Syros Pharmaceuticals. November 12, 2024. Accessed November 13, 2024. https://tinyurl.com/yc25jw9d
Tamibarotene plus azacitidine in participants with newly diagnosed RARA-positive higher-risk myelodysplastic syndrome. ClinicalTrials.gov. Updated November 12, 2024. Accessed November 13, 2024. https://clinicaltrials.gov/study/NCT04797780?term=SELECT-MDS-1&rank=2
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