Syros Pharmaceuticals Advances Clinical Programs in MDS, AML, and APL
核心洞察
Syros Pharmaceuticals remains on track to complete enrollment in the SELECT-MDS (搜索)-1 trial by Q4 2023 and announce pivotal complete response data in Q3 2024.
The SELECT-MDS (搜索)-1 trial protocol was amended to include overall survival as a key secondary endpoint, potentially streamlining the path to full approval.
Initial data from the randomized Phase II trial of tamibarotene in AML (搜索) are expected in Q4 2023, with additional data in 2024.
Syros Pharmaceuticals is making significant strides in its clinical programs targeting hematologic malignancies, including myelodysplastic syndrome (MDS (搜索)), acute myeloid leukemia (AML (搜索)), and acute promyelocytic leukemia (APL (搜索)). The company highlighted progress on its SELECT-MDS-1 trial, an ongoing Phase III study evaluating the combination of tamibarotene and azacitidine in newly diagnosed higher-risk MDS patients with RARA (搜索) overexpression.
SELECT-MDS-1 Trial Update
The SELECT-MDS (搜索)-1 trial is a double-blind, placebo-controlled study. Syros recently amended the study protocol to include overall survival (OS) as a key secondary endpoint, alongside the primary endpoint of complete response (CR). This amendment has the potential to convert an accelerated approval based on CR to a full approval based on OS, if warranted, using an efficient one-trial design. Enrollment of the initial 190 patients is expected to be completed in the fourth quarter of this year, with pivotal CR data anticipated in the third quarter of 2024. The trial will enroll a total of 550 newly diagnosed higher-risk MDS patients to power the study for the key secondary endpoint.
David Roth, Chief Medical Officer of Syros, stated that the use of a single randomized controlled trial to support potential accelerated approval and subsequent conversion to a full approval is consistent with recently issued draft FDA guidance on clinical trial considerations. The existing standard of care, hypomethylating agents (HMAs), offer only a 17% complete response rate and a median survival of 18.6 months.
Tamibarotene in AML
Syros has initiated the randomized portion of the Phase II trial evaluating tamibarotene in combination with venetoclax and azacitidine (ven/aza) in newly diagnosed unfit AML (搜索) patients with RARA (搜索) overexpression. Initial data from this trial are expected in the fourth quarter of this year, followed by additional data in 2024. In the safety lead-in portion of SELECT-AML-1, the triplet combination of tamibarotene and ven/aza demonstrated an 83% CR/CRI rate with a rapid onset of action and no evidence of increased toxicity relative to historical data with ven/aza.
2101 in APL
Syros is also developing 2101, a novel oral form of arsenic trioxide (ATO), for the frontline treatment of APL (搜索). The current standard treatment regimen with intravenous ATO creates a significant burden for patients, involving up to 140 treatment infusions, each over 2 to 4 hours for nearly a year. The company expects to provide an update on the dose confirmation study in the second half of this year to describe the planned development path and timing for further evaluation of 2101 in a registration-enabling study in APL.
Financial Position
Syros reported $3 million in revenue in the first quarter of 2023, and the company believes its current cash position will be sufficient to fund its anticipated operating expenses and capital expenditure requirements into 2025.