Syros Updates SELECT-AML-1 Phase 2 Trial

Syros Pharmaceuticals, a biopharmaceutical company focused on improving treatments for hematologic cancers, has decided to halt enrollment in its SELECT-AML-1 Phase 2 clinical trial. This trial was assessing the efficacy of a triplet regimen consisting of tamibarotene, venetoclax, and azacitidine compared to a doublet regimen of just venetoclax and azacitidine in newly diagnosed, unfit acute myeloid leukemia (AML) patients with overexpression of the RARA gene. The decision follows the results of a predetermined interim analysis.

On August 9, 2024, data from 51 patients enrolled in SELECT-AML-1 were reviewed. This review included a predefined non-binding futility analysis performed on the first 40 randomized patients after the fortieth patient had received approximately three months of treatment or had discontinued the study drug. The analysis revealed a similar rate of complete response (CR) or complete response with incomplete hematologic recovery (CRi) in both the triplet therapy arm (65%) and the doublet therapy arm (70%). Given these results, the likelihood of demonstrating superiority of the triplet regimen in the final analysis with 80 patients was considered low, leading Syros to discontinue further patient enrollment. Notably, no new safety concerns were identified with the triplet therapy. Patients currently participating in the trial will be allowed to continue at the discretion of the study investigators. Data from this trial will be presented at the 12th Annual Meeting of the Society of Hematologic Oncology (SOHO) in September 2024.

Dr. David A. Roth, Chief Medical Officer of Syros, expressed disappointment in the unexpected trial outcome, especially for AML patients. He emphasized that prior Phase 2 trials demonstrated a 61% CR/CRi rate with the combination of tamibarotene and azacitidine in newly diagnosed AML patients with RARA overexpression. This has reinforced Syros' commitment to pursuing a doublet strategy in higher-risk myelodysplastic syndrome (MDS), where they are comparing tamibarotene and azacitidine to azacitidine alone. Syros is dedicated to advancing tamibarotene for the treatment of higher-risk MDS and plans to share pivotal data from the SELECT-MDS-1 trial by mid-fourth quarter of 2024.

Moreover, Syros is actively evaluating tamibarotene, an oral, selective retinoic acid receptor alpha (RARα) agonist, in combination with azacitidine in the SELECT-MDS-1 Phase 3 clinical trial. This trial involves newly diagnosed higher-risk MDS patients with RARA gene overexpression. The SELECT-MDS-1 trial successfully passed a prespecified futility analysis in the first quarter of 2024 and is proceeding as planned, with critical CR data expected by the middle of the fourth quarter of 2024.

Syros Pharmaceuticals remains committed to developing new standards of care for patients with hematologic malignancies, particularly those with blood disorders that have been challenging to treat with other targeted approaches. The company's focus on tamibarotene reflects its mission to improve patient outcomes in these difficult-to-treat conditions.