Shattuck Labs to Present Additional Data From the Phase 1B Dose Expansion Clinical Trial of SL-172154 With Azacitidine (AZA) in Frontline Higher-Risk Myelodysplastic Syndromes (HR-MDS) and TP53 Mutant (TP53m) Acute Myeloid Leukemia (AML) Patients at the European Hematology Association (EHA) 2024 Congress
– Observed encouraging complete response (CR) rates as of the February 1, 2024, data cutoff in previously untreated HR-MDS and TP53m AML patients; successfully bridged responding TP53m AML patients to hematopoietic cell transplantation –
– SL-172154 continued to demonstrate an acceptable safety profile in combination with AZA –
– EHA poster presentation to include additional data from the next planned data cutoff in the second quarter of 2024 –
AUSTIN, TX and DURHAM, NC, May 14, 2024 (GLOBE NEWSWIRE) -- Shattuck Labs, Inc. (Shattuck) (Nasdaq: STTK), a clinical-stage biotechnology company pioneering the development of bifunctional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, today announced the presentation of additional data from the Phase 1B dose expansion clinical trial of SL-172154 with AZA in frontline HR-MDS and TP53m AML patients. These data will be featured in a poster presentation at the EHA 2024 Congress, being held June 13-16, 2024, both virtually and in Madrid, Spain.
"We are rapidly progressing in our clinical development of SL-172154. After completing initial enrollment in the fourth quarter of 2023, we elected to expand both the frontline HR-MDS and TP53m AML cohorts this year," said Dr. Lini Pandite, MBChB, M.B.A., Chief Medical Officer of Shattuck. "The complete response rate in HR-MDS increased by the February 1st data cutoff, and the ORR increased in the TP53m AML cohort. This is encouraging because many patients were still early in their course of treatment. With the next planned data cutoff in the late second quarter of 2024, we are well positioned to provide an update at the EHA Annual Congress. We believe these data will further underscore the therapeutic potential of SL-172154 for patients with previously untreated HR-MDS and TP53m AML."
The full abstract (#P773) is accessible on the EHA Congress portal, and additional details are provided below.
Title: Phase 1B Study of SL-172154, a Bi-functional Fusion Protein Targeting CD47 and CD40, with Azacitidine in Previously Untreated Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndromes
Presenter: Dr. Amer Zeidan
Format: Poster Presentation
Date and Time: June 14th at 18:00 CEST
Key Takeaways from Phase 1B Trial of SL-172154 in Frontline HR-MDS and TP53m AML
Key takeaways: Interim efficacy as of February 1, 2024 observed for SL-172154 in combination with AZA in frontline HR-MDS and TP53m AML. EHA poster presentation to include additional data from the next planned cutoff in the second quarter of 2024.
HR-MDS: In 23 evaluable patients (20 had TP53m, 21 had complex karyotype, and seven had therapy-related MDS), the objective response rate (ORR) was 65%.
TP53m AML: In 14 evaluable patients (11 of whom had secondary AML) the ORR was 36%. A total of 21 patients will be included in the final pre-conference data cutoff.
Two patients achieved a CR, the median time to CR was 8.7 weeks. Another patient achieved a CR with incomplete hematologic recovery (CRi) and two patients achieved a partial response (PR). None of the responders progressed as of the data cutoff.
Four responders (one CR, one CRi, two PR) were taken to hematopoietic cell transplantation (HCT)
Six patients were still undergoing treatment, including one patient in CR.
Median duration of response and overall survival has not been reached in both HR-MDS and TP53m AML as of the data cutoff date.
Safety: SL-172154 had an acceptable safety profile: Infusion-related reactions (IRRs) were the most common SL-172154 related treatment-emergent adverse events (TEAEs).
IRR was reported in 18 patients (46%); all were Grade 1 and 2 except for two Grade 3 events. Other SL-172154 related TEAEs (>=10%) were fatigue in five patients (13%) and hypokalemia in four patients (10%).
Cytokine release syndrome was reported in two patients with HR-MDS (Grade 2 and Grade 3, respectively).
11 patients (28%) experienced at least one Grade 3/4 SL-172154 related TEAE, with fatigue, febrile neutropenia, and IRR as the most common (in two patients each).
Two patients had drug discontinuation that were possibly related to SL-172154: one patient had a Grade 4 event of myocardial infarction, and one patient had a Grade 5 event of cardiac arrest. Both patients had a history of significant cardiovascular disease, adverse risk factors and other comorbidities.
About SL-172154
SL-172154 (SIRPα-Fc-CD40L) is an investigational ARC fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancer. Multiple Phase 1 clinical trials are ongoing for patients with platinum-resistant ovarian cancer (NCT04406623, NCT05483933) and patients with AML and HR-MDS (NCT05275439).
Shattuck Labs 將在 2024 年歐洲血液學協會 (EHA) 大會上公佈 SL-172154 與阿扎西替丁 (AZA) 用於一線高風險骨髓增生異常綜合徵 (HR-MDS) 和 TP53 突變體 (TP53m) 急性髓系白血病 (AML) 患者的 1B 期劑量擴展臨床試驗的更多數據
— 截至2024年2月1日,觀察到令人鼓舞的完全反應(CR)率,此前未經治療的HR-MDS和Tp53m AML患者的數據截止率;成功地將反應的tp53m AML患者與造血細胞移植聯繫起來—
— SL-172154 與 AZA 結合使用時繼續表現出可接受的安全狀況 —
— EHA海報演示文稿將包括來自2024年第二季度下一個計劃數據截止日期的更多數據—
德克薩斯州奧斯汀和北卡羅來納州達勒姆,2024 年 5 月 14 日(GLOBE NEWSWIRE)—— Shattuck Labs, Inc. (Shattuck)(納斯達克股票代碼:STTK)是一家臨床階段的生物技術公司,率先開發雙功能融合蛋白作爲一種治療癌症和自身免疫性疾病患者的新生物藥物,今天宣佈公佈了使用 AZA 進行的 SL-172154 1B 期劑量擴展臨床試驗的更多數據一線 HR-MDS 和 Tp53m 急性髓細胞白血病患者。這些數據將在2024年6月13日至16日舉行的EHA 2024年大會的海報展示中,既有虛擬會議也有在西班牙馬德里舉行。
“我們的 SL-172154 臨床開發正在迅速取得進展。在2023年第四季度完成初始註冊後,我們選擇在今年擴大一線HR-MDS和Tp5300萬反洗錢隊伍。” 沙特克首席醫學官、工商管理碩士MBChB、工商管理碩士利尼·潘迪特博士說。“截至2月1日的數據截止日期,HR-MDS的完全回覆率有所提高,而Tp53m AML隊列的ORR也有所增加。這令人鼓舞,因爲許多患者仍處於治療初期。下一次計劃在2024年第二季度末截止數據,我們完全有能力在EHA年度大會上提供最新情況。我們相信,這些數據將進一步強調 SL-172154 對以前未經治療的 HR-MDS 和 tP53m 急性髓細胞白血病患者的治療潛力。”
完整摘要 (#P773) 可在EHA會議門戶網站上查閱,其他詳細信息見下文。
一線 HR-MDS 和 TP53m 反洗錢中 SL-172154 1B 期試驗的關鍵要點
關鍵要點:截至 2024 年 2 月 1 日,在前線 HR-MDS 和 tp53m 急性髓細胞白血病中觀察到 SL-172154 與 AZA 聯合使用的中期療效。EHA海報展示將包括2024年第二季度下一個計劃截止日期的更多數據。
HR-MDS:在23名可評估的患者(20名患有tp53m,21名患有複雜的核型,7名患有與治療相關的MDS)中,客觀緩解率(ORR)爲65%。
tP53m 急性髓細胞白血病:在14名可評估的患者(其中11名患有繼發性急性髓細胞白血病)中,ORR爲36%。總共21名患者將包括在最終的會前數據截止日期中。
兩名患者獲得了 CR,CR 的中位時間爲 8.7 周。另一名患者在血液學恢復不完全(CRi)的情況下獲得了 CR,兩名患者實現了部分反應(PR)。截至數據截止時,所有響應者均未取得進展。
四名受試者(一個 CR、一個 CRi、兩個 PR)被帶到造血細胞移植(HCT)
六名患者仍在接受治療,其中包括一名正在接受CR的患者。
截至數據截止日期,HR-MDS和TP53m AML均未達到中位反應持續時間和總存活率。
安全性:SL-172154 具有可接受的安全性:輸液相關反應 (IRR) 是最常見的 SL-172154 相關治療緊急不良事件 (TEAE)。
18名患者報告了IRR(46%);除兩起3級事件外,所有患者均爲1級和2級。其他 SL-172154 相關的 TEAE(>= 10%)是五名患者的疲勞(13%)和四名患者的低鉀血癥(10%)。
在兩名HR-MDS患者(分別爲2級和3級)中報告了細胞因子釋放綜合徵。
11 名患者(28%)經歷了至少一次 3/4 級 SL-172154 相關的 TEAE,其中最常見的是疲勞、發熱性中性粒細胞減少和 IRR(每例患者中有兩例)。
兩名患者的停藥可能與 SL-172154 有關:一名患者出現 4 級心肌梗塞事件,一名患者出現 5 級心臟驟停事件。兩名患者都有嚴重的心血管疾病、不良風險因素和其他合併症的病史。
關於 SL-172154
SL-172154(SIRPα-FC-CD40L)是一種研究中的ARC融合蛋白,旨在同時抑制CD47/SIRPα檢查點相互作用並激活CD40共刺激受體,以增強晚期癌症患者的抗腫瘤免疫反應。針對鉑耐藥卵巢癌(NCT04406623、NCT05483933)患者以及急性髓細胞白血病和HR-MDS(NCT05275439)患者的多項1期臨床試驗正在進行中。