Syros Pharmaceuticals announced strong and encouraging initial data from its ongoing SELECT-AML-1 Phase 2 trial evaluating tamibarotene, an oral, selective, retinoic acid receptor alpha (RARa) agonist, in combination with venetoclax and azacitidine in newly diagnosed, unfit patients with acute myeloid leukemia (AML) and RARA gene overexpression. Initial Data from SELECT-AML-1 Phase 2 Trial: SELECT-AML-1 is evaluating the safety and efficacy of tamibarotene in combination with venetoclax and azacitidine compared to venetoclax and azacitidine in approximately 80 patients randomized 1:1. The trial is also evaluating the triplet regimen as a salvage strategy in patients in the control arm who do not respond to venetoclax and azacitidine. The primary endpoint of the trial is complete response rate (CR)/complete response with incomplete hematologic recovery (CRi).

In December 2022, Syros reported data from the safety lead-in portion of SELECT-AML-1, in which five of six response evaluable patients (83%) achieved CR/CRi. As of November 13, 2023, 23 newly diagnosed unfit AML patients positive for RARA overexpression had enrolled in the randomized portion of the trial, including 19 who were evaluable for response. The median age of the patients for the triplet arm was 77 (ranging from 66-85) and the median age of the patients for the doublet arm was 76 (ranging from 69-84).

Clinical Activity Data: The primary endpoint (CR/CRi rate), defined in alignment with ELN AML criteria (Dohner 2017 and Bloomfield 2018), was 100% among response evaluable patients (nine of nine) treated with the combination of tamibarotene, venetoclax and azacitidine, as compared to 70% of patients (seven of ten) treated with the control (venetoclax and azacitidine alone). Safety Data: Consistent with prior clinical experience from the safety lead-in portion of this study, tamibarotene administered in combination with approved doses of venetoclax and azacitidine was generally well tolerated, and the overall safety profile demonstrated no additive toxicities or new safety signals, or evidence of increased myelosuppression compared to treatment with the doublet combination of venetoclax and azacitidine. The majority of non-hematologic adverse events (AEs) were low-grade and reversible, and rates of serious adverse events (SAEs) were comparable between the study arms. The company continues to enroll patients in SELECT-AML-1 and anticipates reporting updated data from the trial in 2024.