On August 12, 2024 Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, reported that it will discontinue enrollment in the SELECT-AML-1 Phase 2 clinical trial evaluating the triplet regimen of tamibarotene in combination with venetoclax and azacitidine compared to the doublet regimen of venetoclax and azacitidine in newly diagnosed, unfit patients with acute myeloid leukemia (AML) and RARA gene overexpression (Press release, Syros Pharmaceuticals, AUG 12, 2024, View Source [SID1234645738]). This decision is based on the results of a prespecified interim analysis of the trial.

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Data from 51 patients enrolled in SELECT-AML-1 were reviewed on August 9, 2024. This review included a prespecified non-binding futility analysis conducted on the first 40 randomized patients after the fortieth randomized patient received approximately three months of study drug or discontinued treatment. A similar complete response (CR)/complete response with incomplete hematologic recovery (CRi) rate was observed in the triplet arm (n=20; 65%, CI: 40.8-84.6) and the doublet arm (n=20; 70%, CI: 45.7-88.1). As a result, the probability for success of the SELECT-AML-1 study to demonstrate superiority at the final analysis in 80 randomized patients was considered low, and Syros made the decision to discontinue further enrollment. There were no new safety signals associated with the use of tamibarotene in combination with venetoclax and azacitidine. Patients currently enrolled in SELECT-AML-1 will have the opportunity to remain on study at the discretion of study investigators. Syros plans to present data from SELECT-AML-1 at the 12th Annual Meeting of the Society of Hematologic Oncology (SOHO) in September 2024.

"We are disappointed by this unexpected outcome, especially for people living with AML," said David A. Roth, M.D., Chief Medical Officer of Syros. "In our prior Phase 2 clinical trial, the doublet combination of tamibarotene and azacitidine delivered a 61% CR/CRi rate in newly diagnosed AML patients with RARA overexpression. This supports our conviction in pursuing a doublet strategy in higher-risk MDS, where we are comparing tamibarotene and azacitidine to azacitidine alone. We remain steadfast in our commitment to delivering tamibarotene for the treatment of HR-MDS and look forward to sharing pivotal data from SELECT-MDS-1 by mid-fourth quarter."

Syros continues to evaluate tamibarotene, an oral, selective, retinoic acid receptor alpha (RARα) agonist, in combination with azacitidine in the SELECT-MDS-1 Phase 3 clinical trial in newly diagnosed higher-risk myelodysplastic syndrome (MDS) patients with RARA gene overexpression. The SELECT-MDS-1 trial passed a prespecified futility analysis in the first quarter of 2024 and is continuing as planned, with pivotal CR data expected by the middle of the fourth quarter of 2024.