Syros Reveals Promising Progress in SELECT-AML-1 Phase 2 Clinical Trial

Syros Pharmaceuticals, a biopharmaceutical firm dedicated to establishing innovative care standards for hematologic malignancies, has announced the cessation of patient enrollment in the SELECT-AML-1 Phase 2 clinical trial. This trial was investigating the efficacy of a triplet therapy comprising tamibarotene, venetoclax, and azacitidine versus a doublet regimen of venetoclax and azacitidine for newly diagnosed, unfit patients with acute myeloid leukemia (AML) and RARA gene overexpression. The decision follows an interim analysis of the trial's results.

On August 9, 2024, data from 51 participants in the SELECT-AML-1 trial were evaluated. This included a prespecified non-binding futility analysis of the first 40 randomized patients after the fortieth participant had either received approximately three months of the study drug or had withdrawn from treatment. The analysis revealed comparable complete response (CR) and complete response with incomplete hematologic recovery (CRi) rates between the triplet (n=20; 65%, CI: 40.8-84.6) and doublet (n=20; 70%, CI: 45.7-88.1) groups.

Consequently, Syros concluded that the likelihood of demonstrating superiority in the final analysis involving 80 randomized patients was low, prompting the decision to halt further enrollment. There were no new safety concerns linked to the use of tamibarotene alongside venetoclax and azacitidine. Patients currently participating in SELECT-AML-1 will have the option to continue their involvement at the discretion of the study investigators. Syros intends to present the findings from SELECT-AML-1 at the upcoming 12th Annual Meeting of the Society of Hematologic Oncology (SOHO) in September 2024.

David A. Roth, M.D., Chief Medical Officer of Syros, said, “We are disappointed by this unexpected outcome, especially for people living with AML. 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 is actively investigating tamibarotene, an oral selective agonist of the retinoic acid receptor alpha (RARα), in conjunction with azacitidine in the SELECT-MDS-1 Phase 3 clinical trial. This study focuses on newly diagnosed patients with higher-risk myelodysplastic syndrome (MDS) exhibiting RARA gene overexpression. The SELECT-MDS-1 trial successfully cleared a prespecified futility analysis in the first quarter of 2024 and will proceed as intended, with critical complete response (CR) data anticipated by mid-fourth quarter of 2024.