Delving into the Latest Updates on BEBT-908 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

双利司他, CUDC 908, CUDC-908

+ [2]

Target

HDACs x PI3Ks

Action

inhibitors

Mechanism

HDAC inhibitors(Histone deacetylase inhibitors), PI3K family inhibitors(Phosphatidylinositol 3-kinase family inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [4]

Active Indication

Diffuse large B-cell lymphoma recurrentDiffuse large B-cell lymphoma refractoryPeripheral T-Cell Lymphoma+ [8]

Inactive Indication

Multiple MyelomaRecurrent LymphomaRefractory Lymphoma

Originator Organization

BeBetter Med, Inc.

Active Organization

Zhongshan Union Weihua Pharmaceutical Co. Ltd.

BeBetter Med, Inc.

Inactive Organization-

License Organization

Curis, Inc.

BeBetter Med, Inc.

Drug Highest PhaseNDA/BLA

First Approval Date-

RegulationPriority Review (China), Breakthrough Therapy (China)

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Structure/Sequence

Molecular FormulaC23H28Cl3N9O3S

InChIKeyXQJBSJNJWWXTFM-UHFFFAOYSA-N

CAS Registry1646906-27-5

This is a multicenter, randomized, controlled, open-label Phase III clinical trial, aimed at evaluating the efficacy and safety of BEBT-908 combined with rituximab (R) compared to investigator-selected standard chemotherapy regimens [Standard of Care (SOC)] [i.e., rituximab-gemcitabine-oxaliplatin (R-GemOx) or rituximab-ifosfamide-carboplatin-etoposide (R-ICE)] for the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL).

Start Date06 Jan 2025

Sponsor / Collaborator

BeBetter Med, Inc.

CTR20244220

/ RecruitingPhase 3

BEBT-908联合利妥昔单抗（R）对比利妥昔单抗-吉西他滨-奥沙利铂（R-GemOx）或利妥昔单抗-异环磷酰胺-卡铂-依托泊苷（R-ICE）治疗复发/难治性弥漫性大B细胞淋巴瘤（r/r DLBCL）有效性和安全性的多中心、随机、对照、开放性III期临床研究

[Translation] A multicenter, randomized, controlled, open-label phase III clinical study on the efficacy and safety of BEBT-908 combined with rituximab (R) versus rituximab-gemcitabine-oxaliplatin (R-GemOx) or rituximab-ifosfamide-carboplatin-etoposide (R-ICE) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL)

主要目的：评价BEBT-908联合R对比R-GemOx或R-ICE治疗r/r DLBCL的总生存期（OS）。次要目的：评价BEBT-908联合R对比R-GemOx或R-ICE治疗r/r DLBCL由独立影像评估委员会（IRC）评估的无进展生存期（PFS），作为第一次要终点指标；BEBT-908联合R对比R-GemOx或R-ICE治疗r/r DLBCL由研究者评估的无进展生存期（PFS）以及由研究者和独立影像评估委员会评估的总缓解率（ORR）、完成治疗后总缓解率（ORR-EoT）、临床获益率（CBR）和缓解持续时间（DoR）；评价BEBT-908联合R对比R-GemOx或R-ICE治疗r/r DLBCL的安全性。

[Translation]

Primary objective: To evaluate the overall survival (OS) of BEBT-908 combined with R vs. R-GemOx or R-ICE in the treatment of r/r DLBCL. Secondary objectives: To evaluate the progression-free survival (PFS) assessed by the independent imaging review committee (IRC) of BEBT-908 combined with R vs. R-GemOx or R-ICE in the treatment of r/r DLBCL as the first secondary endpoint; the progression-free survival (PFS) assessed by the investigator and the overall response rate (ORR), the overall response rate after completion of treatment (ORR-EoT), the clinical benefit rate (CBR) and the duration of response (DoR) of BEBT-908 combined with R vs. R-GemOx or R-ICE in the treatment of r/r DLBCL as assessed by the investigator and the independent imaging review committee; to evaluate the safety of BEBT-908 combined with R vs. R-GemOx or R-ICE in the treatment of r/r DLBCL.

Start Date26 Dec 2024

Sponsor / Collaborator

BeBetter Med, Inc.

CTR20244090

/ CompletedPhase 1

[14C]注射用BEBT-908在中国成年男性健康受试者体内的物质平衡研究

[Translation] Study on the material balance of [14C]BEBT-908 for injection in healthy adult male subjects in China

主要目的： 1.定量分析男性健康受试者[14C]注射用BEBT-908后排泄物中的总放射性，获得人体放射性总回收率、排泄数据和主要排泄途径； 2.定量分析男性健康受试者[14C]注射用BEBT-908后全血和血浆中的总放射性，获得全血和血浆总放射性的药代动力学参数，考察全血和血浆中总放射性的分配情况； 3.定量分析男性健康受试者[14C]注射用BEBT-908后人血浆、尿液和粪便的放射性代谢物谱，鉴定主要代谢产物，确定[14C]BEBT-908在人体内的代谢途径。次要目的： 1.采用经验证的方法定量分析血浆中BEBT-908及其代谢产物（如适用）的浓度，获得血浆中BEBT-908及其代谢产物（如适用）的药代动力学参数； 2.观察男性健康受试者单次静脉给[14C]注射用BEBT-908后的安全性。

[Translation]

Primary objectives: 1. To quantitatively analyze the total radioactivity in the excreta after [14C]BEBT-908 injection in male healthy subjects, and obtain the total recovery rate of human radioactivity, excretion data and main excretion pathways; 2. To quantitatively analyze the total radioactivity in the whole blood and plasma after [14C]BEBT-908 injection in male healthy subjects, obtain the pharmacokinetic parameters of the total radioactivity in whole blood and plasma, and investigate the distribution of the total radioactivity in whole blood and plasma; 3. To quantitatively analyze the radioactive metabolite profiles in human plasma, urine and feces after [14C]BEBT-908 injection in male healthy subjects, identify the main metabolites, and determine the metabolic pathway of [14C]BEBT-908 in the human body. Secondary objectives: 1. To quantitatively analyze the concentration of BEBT-908 and its metabolites (if applicable) in plasma using a validated method, and obtain the pharmacokinetic parameters of BEBT-908 and its metabolites (if applicable) in plasma; 2. To observe the safety of male healthy subjects after a single intravenous administration of [14C]BEBT-908 for injection.

Start Date11 Dec 2024

Sponsor / Collaborator

BeBetter Med, Inc.

100 Clinical Results associated with BEBT-908

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100 Translational Medicine associated with BEBT-908

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100 Patents (Medical) associated with BEBT-908

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4

Literatures (Medical) associated with BEBT-908

01 Nov 2023·Targeted oncology

Dual PI3K/HDAC Inhibitor BEBT-908 Exhibits Potent Efficacy as Monotherapy for Primary Central Nervous System Lymphoma

Article

Author: Zhou, Minhua ; Wang, Ning ; Pan, Lu ; Xiong, Yan ; Chen, Feili ; Li, Wenyu ; Fan, Fushun ; Qian, Changgeng ; Mo, Zhenxian ; Cai, Xiong ; Liu, Xinjian ; Ye, Xiaolan

BACKGROUND:

The efficacy of systemic treatment for primary central nervous system lymphoma (PCNSL) is limited because of the blood-brain barrier (BBB) and the ineffectiveness of chemotherapy. The dual PI3K/HDAC inhibitor BEBT-908 has exhibited favorable in vivo distribution and activity in various cancers.

OBJECTIVES:

The aims of this study were to assess the efficacy of BEBT-908 in brain orthotopic mouse models of hematological malignancies, to investigate its pharmacologic properties, and to elucidate the underlying mechanism of action.

METHODS:

We evaluated the anticancer activity of BEBT-908 in various hematological malignancies through cell viability assays. The impact of BEBT-908 on c-Myc expression and ferroptosis signaling pathways was assessed using Western blotting, qPCR, ROS detection, GSH/GSSG detection, and IHC. Pharmacokinetic and pharmacodynamic profiles were assessed through LC-MS/MS and Western blotting. The effects of BEBT-908 in vivo were examined using xenografts and brain orthotopic mouse models.

RESULTS:

Our findings demonstrate that BEBT-908 exhibits promising anti-tumor activity in vitro and in vivo across multiple subtypes of hematological malignancies. Furthermore, BEBT-908 exhibits excellent BBB penetration and inhibits tumor growth in a brain orthotopic lymphoma model with prolonged survival of host mice. Mechanistically, BEBT-908 downregulated c-Myc expression, which contributed to ferroptosis, ultimately leading to tumor shrinkage.

CONCLUSION:

Our study provides robust evidence for the dual PI3K/HDAC inhibitor BEBT-908 as an effective anti-cancer agent for PCNSL.

15 Dec 2021·Cancer researchQ1 · MEDICINE

A Dual PI3K/HDAC Inhibitor Induces Immunogenic Ferroptosis to Potentiate Cancer Immune Checkpoint Therapy

Q1 · MEDICINE

Article

Author: Bao, Rudi ; Zhou, Minhua ; Chen, Jian ; Liu, Haiqi ; Liu, Xinjian ; Qian, Changgeng ; Mo, Zhenxian ; Cai, Xiong ; Liu, Pei ; Ma, Yaru ; Zhou, Yiping ; Fan, Fushun

Abstract:

The capacity of targeted anticancer agents to exert immunomodulatory effects provides a strong rationale to develop novel agents suitable for combinatorial regimens with immunotherapy to improve clinical outcomes. In this study, we developed a dual-targeting PI3K and HDAC inhibitor BEBT-908 that potently inhibits tumor cell growth and potentiates anti-PD1 therapy in mice by inducing immunogenic ferroptosis in cancer cells. Treatment with BEBT-908 promoted ferroptotic cell death of cancer cells by hyperacetylating p53 and facilitating the expression of ferroptotic signaling. Furthermore, BEBT-908 promoted a proinflammatory tumor microenvironment that activated host antitumor immune responses and potentiated immune checkpoint blockade therapy. Mechanistically, BEBT-908–induced ferroptosis led to upregulation of MHC class I and activation of endogenous IFNγ signaling in cancer cells via the STAT1 signaling pathway. The dual PI3K/HDAC inhibitor BEBT-908 is a promising targeted therapeutic agent against multiple cancer types that promotes immunogenic ferroptosis and enhances the efficacy of immunotherapy.

Significance::

The dual PI3K/HDAC inhibitor BEBT-908 elicits potent antitumor responses, effectively inducing immunogenic ferroptosis of tumor cells and potentiating cancer immunotherapy.

01 Mar 2018·Biochemical and biophysical research communicationsQ3 · BIOLOGY

Retraction notice to “BEBT-908: A novel potent PI3K/HDAC inhibitor against diffuse large B-cell lymphoma” [Biochem. Biophys. Res. Commun. 491 (2017) 939-945]

Q3 · BIOLOGY

Article

Author: Li, Jin ; Qian, Changgeng ; Yi, Pingyong ; Zhou, Qianqian ; Li, Jiwei ; Li, Kunlun

This article has been retracted.

100 Deals associated with BEBT-908

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diffuse large B-cell lymphoma recurrent	NDA/BLA	China	Zhongshan Union Weihua Pharmaceutical Co. Ltd.	09 Oct 2023
Diffuse large B-cell lymphoma recurrent	NDA/BLA	China	BeBetter Med, Inc.	09 Oct 2023
Diffuse large B-cell lymphoma refractory	NDA/BLA	China	Zhongshan Union Weihua Pharmaceutical Co. Ltd.	09 Oct 2023
Diffuse large B-cell lymphoma refractory	NDA/BLA	China	BeBetter Med, Inc.	09 Oct 2023
Advanced Lung Non-Small Cell Carcinoma	Phase 2	China	BeBetter Med, Inc.	28 Mar 2022
Hormone receptor positive HER2 negative breast cancer	Phase 2	China	BeBetter Med, Inc.	23 Feb 2022
Peripheral T-Cell Lymphoma	Phase 2	China	BeBetter Med, Inc.	16 Aug 2021
Chronic Lymphocytic Leukemia	Phase 2	China	BeBetter Med, Inc.	12 Aug 2021
Follicular Lymphoma	Phase 2	China	BeBetter Med, Inc.	12 Aug 2021
Marginal Zone B-Cell Lymphoma	Phase 2	China	BeBetter Med, Inc.	12 Aug 2021