A Multi-Site Break Through Cancer Trial: Phase II Study Investigating Dual Inhibition of BCL2 and Menin in AML MRD Using the Combination of Venetoclax and Revumenib

To learn if the combination of venetoclax and revumenib can help to control MRD-positive AML.

开始日期2024-09-23

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+2]

NCT06313437 / Not yet recruiting临床1期IIT

A Phase I Trial of Revumenib in Combination With 7+3 (7 Days of Cytarabine and 3 Days of Daunorubicin) + Midostaurin Induction Chemotherapy for the Frontline Treatment of NPM1 and FLT3 Mutated AML

This research is being conducted to determine a safe and effective dose of revumenib that can be given in combination with standard induction (initial therapy to induce a remission) + FLT3 targeted therapy (midostaurin) and a single cycle of post-remission therapy + FLT3 targeted therapy (midostaurin) to participants with newly diagnosed Nucleophosmin (NPM1) and FMS-like tyrosine kinase 3 (FLT3) mutated Acute Myeloid Leukemia (AML).
The names of the study drugs involved in this study are:
Revumenib (SNDX-5613) (a type of menin inhibitor)
Midostaurin (a type of multi-kinase including FLT3 inhibitor)
Cytarabine (a type of antineoplastic agent)
Daunorubicin (a type of antineoplastic agent)

开始日期2024-09-01

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+1]

NCT06229912 / Recruiting临床2期IIT

A Phase II Study of the Menin Inhibitor Revumenib in Leukemia Associated With Upregulation of HOX Genes

To learn if revumenib (also known as SNDX-5613) can help to control leukemias associated with an increase in expression of HOX genes.

开始日期2024-07-31

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

100 项与 Syndax Pharmaceuticals, Inc. 相关的临床结果

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0 项与 Syndax Pharmaceuticals, Inc. 相关的专利（医药）

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项与 Syndax Pharmaceuticals, Inc. 相关的文献（医药）

2024-09-19·NEW ENGLAND JOURNAL OF MEDICINE

Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease

Article

作者: Ordentlich, Peter ; Arai, Sally ; Choe, Hannah ; Alousi, Amin ; Bermúdez, Arancha ; Pusic, Iskra ; White, Jennifer ; Hamadani, Mehdi ; Kitko, Carrie L ; Chhabra, Saurabh ; Wolff, Daniel ; O'Toole, Timothy ; Lee, Stephanie J ; Tian, Chuan ; DeFilipp, Zachariah ; Radojcic, Vedran ; Perez-Simon, Jose A ; Socié, Gerard ; Salhotra, Amandeep ; Kim, Inho ; Kwon, Mi ; Bittencourt, Henrique ; Cutler, Corey

BACKGROUND:

Colony-stimulating factor 1 receptor (CSF1R)-dependent monocytes and macrophages are key mediators of chronic graft-versus-host disease (GVHD), a major long-term complication of allogeneic hematopoietic stem-cell transplantation. The CSF1R-blocking antibody axatilimab has shown promising clinical activity in chronic GVHD.

METHODS:

In this phase 2, multinational, pivotal, randomized study, we evaluated axatilimab at three different doses in patients with recurrent or refractory chronic GVHD. Patients were randomly assigned to receive axatilimab, administered intravenously, at a dose of 0.3 mg per kilogram of body weight every 2 weeks (0.3-mg dose group), at a dose of 1 mg per kilogram every 2 weeks (1-mg dose group), or at a dose of 3 mg per kilogram every 4 weeks (3-mg dose group). The primary end point was overall response (complete or partial response) in the first six cycles; the key secondary end point was a patient-reported decrease in chronic GVHD symptom burden, as assessed by a reduction of more than 5 points on the modified Lee Symptom Scale (range, 0 to 100, with higher scores indicating worse symptoms). The primary end point would be met if the lower bound of the 95% confidence interval exceeded 30%.

RESULTS:

A total of 241 patients were enrolled (80 patients in the 0.3-mg dose group, 81 in the 1-mg dose group, and 80 in the 3-mg dose group). The primary end point was met in all the groups; an overall response was observed in 74% (95% confidence interval [CI], 63 to 83) of the patients in the 0.3-mg dose group, 67% (95% CI, 55 to 77) of the patients in the 1-mg dose group, and 50% (95% CI, 39 to 61) of the patients in the 3-mg dose group. A reduction of more than 5 points on the modified Lee Symptom Scale was reported in 60%, 69%, and 41% of the patients in the three dose groups, respectively. The most common adverse events were dose-dependent transient laboratory abnormalities related to CSF1R blockade. Adverse events leading to discontinuation of axatilimab occurred in 6% of the patients in the 0.3-mg dose group, 22% in the 1-mg dose group, and 18% in the 3-mg dose group.

CONCLUSIONS:

Targeting CSF1R-dependent monocytes and macrophages with axatilimab resulted in a high incidence of response among patients with recurrent or refractory chronic GVHD. (Funded by Syndax Pharmaceuticals and Incyte; AGAVE-201 ClinicalTrials.gov number, NCT04710576.).

2023-04-13·Blood cancer journal

Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1.

Article

作者: Vakoc, Christopher R ; Heffernan, Tim ; Bhalla, Kapil N ; Birdwell, Christine ; Takahashi, Koichi ; Boettcher, Steffen ; McGeehan, Gerard M ; Ruan, Xinjia ; Kadia, Tapan M ; Soth, Michael J ; Fiskus, Warren ; DiNardo, Courtney D ; Mill, Christopher P ; Su, Xiaoping ; Loghavi, Sanam ; Das, Kaberi ; Davis, John A ; Daver, Naval

Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A protein domain-focused CRISPR-Cas9 screen in MLL1-r AML cells identified targetable co-dependencies with MI treatment, including BRD4, EP300, MOZ and KDM1A. Consistent with this, in vitro co-treatment with MI and BET, MOZ, LSD1 or CBP/p300 inhibitor induced synergistic loss of viability of AML cells with MLL1-r or mtNPM1. Co-treatment with MI and BET or CBP/p300 inhibitor also exerted significantly superior in vivo efficacy in xenograft models of AML with MLL1-r. These findings highlight novel, MI-based combinations that could prevent escape of AML stem/progenitor cells following MI monotherapy, which is responsible for therapy-refractory AML relapse.

2023-03-01·Nature1区 · 综合性期刊

The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia.

1区 · 综合性期刊

Article

作者: Armstrong, Scott A ; Stein, Eytan M ; Stone, Richard ; Shenoy, Shalini ; Issa, Ghayas C ; Cuglievan, Branko ; Meyers, Michael L ; Perner, Florian ; Dickens, David S ; Perry, Jennifer A ; Thirman, Michael J ; McGeehan, Gerard M ; Rosen, Galit ; Kantarjian, Hagop ; Gu, Yu ; Arellano, Martha ; Smith, Steven ; Aldoss, Ibrahim ; Bagley, Rebecca G ; Kumar, Vinit ; DiPersio, John ; Shukla, Neerav ; Patel, Manish R ; Ordentlich, Peter

Targeting critical epigenetic regulators reverses aberrant transcription in cancer, thereby restoring normal tissue function^1-3. The interaction of menin with lysine methyltransferase 2A (KMT2A), an epigenetic regulator, is a dependence in acute leukaemia caused by either rearrangement of KMT2A or mutation of the nucleophosmin 1 gene (NPM1)^4-6. KMT2A rearrangements occur in up to 10% of acute leukaemias and have an adverse prognosis, whereas NPM1 mutations occur in up to 30%, forming the most common genetic alteration in acute myeloid leukaemia^7,8. Here, we describe the results of the first-in-human phase 1 clinical trial investigating revumenib (SNDX-5613), a potent and selective oral inhibitor of the menin-KMT2A interaction, in patients with relapsed or refractory acute leukaemia (ClinicalTrials.gov, NCT04065399). We show that therapy with revumenib was associated with a low frequency of grade 3 or higher treatment-related adverse events and a 30% rate of complete remission or complete remission with partial haematologic recovery (CR/CRh) in the efficacy analysis population. Asymptomatic prolongation of the QT interval on electrocardiography was identified as the only dose-limiting toxicity. Remissions occurred in leukaemias refractory to multiple previous lines of therapy. We demonstrate clearance of residual disease using sensitive clinical assays and identify hallmarks of differentiation into normal haematopoietic cells, including differentiation syndrome. These data establish menin inhibition as a therapeutic strategy for susceptible acute leukaemia subtypes.

202

项与 Syndax Pharmaceuticals, Inc. 相关的新闻（医药）

2024-11-01

·PRNewswire

Syndax Pharmaceuticals Reports Inducement Grants Under NASDAQ Listing Rule 5635(c)(4)

WALTHAM, Mass., Nov. 1, 2024 /PRNewswire/ -- Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced that on November 1, 2024 the Company granted inducement awards to purchase up to 78,700 shares of common stock to four new employees under the Company's 2023 Inducement Plan. The stock options will vest over four years, with 25% of the underlying shares vesting on the one-year anniversary of the vesting commencement date and 1/48th of the underlying shares vesting monthly thereafter over 36 months, subject to the employee's continued service relationship with Syndax through the applicable vesting dates. About Syndax Syndax Pharmaceuticals is a commercial-stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Highlights of the Company's pipeline include revumenib, a selective menin inhibitor, and Niktimvo™ (axatilimab-csfr), an FDA-approved monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. Fueled by our commitment to reimagining cancer care, Syndax is working to unlock the full potential of its pipeline and is conducting several clinical trials across the continuum of treatment. For more information, please visit or follow the Company on X (formerly Twitter) and LinkedIn. Syndax Contact Sharon Klahre Syndax Pharmaceuticals, Inc. [email protected] Tel 781.684.9827 SOURCE Syndax Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

上市批准

2024-11-01

·PRNewswire

Syndax Announces Participation in November Investor Conferences

WALTHAM, Mass., Nov. 1, 2024 /PRNewswire/ -- Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced that Michael A. Metzger, Chief Executive Officer of Syndax, as well as members of the Syndax management team, will participate in the following upcoming investor conferences: Guggenheim's Inaugural Healthcare Innovation Conference in Boston, MA with a fireside chat on Wednesday, November 13, 2024, at 1:30 p.m. ET UBS Global Healthcare Conference in Ranchos Palos Verdes, CA with a fireside chat on Thursday, November 14, 2024, at 10:15 a.m. ET / 7:15 a.m. PT Stifel 2024 Healthcare Conference in New York, NY with a fireside chat on Monday, November 18, 2024, at 1:50 p.m. ET Jefferies London Healthcare Conference in London, UK, November 20-21, 2024 A live webcast of the fireside chats will be available in the Investor section of the Company's website at , where a replay will also be available for a limited time. About Syndax Syndax Pharmaceuticals is a commercial-stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Highlights of the Company's pipeline include revumenib, a selective menin inhibitor, and Niktimvo™ (axatilimab-csfr), an FDA-approved monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. Fueled by our commitment to reimagining cancer care, Syndax is working to unlock the full potential of its pipeline and is conducting several clinical trials across the continuum of treatment. For more information, please visit or follow the Company on X (formerly Twitter) and LinkedIn. Syndax Contacts Sharon Klahre Syndax Pharmaceuticals, Inc. [email protected] Tel 781.684.9827 SNDX-G SOURCE Syndax Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

上市批准

2024-10-04

·PRNewswire

Syndax Pharmaceuticals Reports Inducement Grants Under NASDAQ Listing Rule 5635(c)(4)

WALTHAM, Mass., Oct. 4, 2024 /PRNewswire/ -- Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced that on October 1, 2024 the Company granted inducement awards to purchase up to 62,700 shares of common stock to five new employees under the Company's 2023 Inducement Plan. The stock options will vest over four years, with 25% of the underlying shares vesting on the one-year anniversary of the vesting commencement date and 1/48th of the underlying shares vesting monthly thereafter over 36 months, subject to the employee's continued service relationship with Syndax through the applicable vesting dates. About Syndax Syndax Pharmaceuticals is a commercial stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Highlights of the Company's pipeline include revumenib, a highly selective menin inhibitor, and Niktimvo™ (axatilimab-csfr), a monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. Syndax is working to unlock the full potential of its pipeline and is conducting several clinical trials across the continuum of treatment for both revumenib and Niktimvo. For more information, please visit or follow the Company on X (formerly Twitter) and LinkedIn. Syndax Contact Sharon Klahre Syndax Pharmaceuticals, Inc. [email protected] Tel 781.684.9827 SOURCE Syndax Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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药物(靶点)	适应症	全球最高研发状态

Revumenib ( MLL1 x menin )	急性淋巴细胞白血病更多	申请上市
Axatilimab-csfr ( CSF-1R )	慢性移植物抗宿主病更多	申请上市
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