A Two-part Phase 1 Open-label Safety and Pharmacokinetic Study of Intravenous RC220 in Combination With Doxorubicin in Adult Patients With Solid Tumours.

This is a multi-centre, two-part, open-label, phase 1, first in human study of multiple ascending doses of RC220 bisantrene formulation alone and in combination with fixed dose doxorubicin to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) in adult patients with advanced solid tumours where an anthracycline may be considered as a treatment option / or is indicated.
The study will consist of Part 1 - dose-escalation, to determine the maximum tolerated combination dose of RC220 with doxorubicin to be evaluated in Part 2 - dose-expansion cohort, in patients with solid tumours that are anthracycline treatment naïve and for whom treatment with doxorubicin is indicated. The objective of Part 2 will be to confirm the safety and tolerability and evaluate the preliminary cardioprotective and anti-tumour efficacy of the maximum tolerated combined dose (MTCD) of RC220 with doxorubicin.

开始日期2025-04-02

申办/合作机构

Race Oncology Ltd.

NCT05456269

/ Withdrawn临床1期

An Open-label Two Strata Study of Bisantrene in Combination With Cytarabine Arabinoside or Bisantrene in Combination With Oral Decitabine/Cedazuridine for the Treatment of Acute Myeloid Leukemia Patients With Extramedullary Disease

This is a two strata Phase 1b study to assess the safety and efficacy of bisantrene (RC110) in combination with a) cytarabine arabinoside (Ara-C) treatment for patients with relapsed or refractory (R/R) Acute Myeloid Leukemia (AML) with extramedullary disease and able to tolerate intensive chemotherapy; b) in combination with decitabine/cedazuridune (ASTX727) new or relapsed or refractory AML or high risk MDS or CMML with extramedullary disease and unable or not willing to have intensive chemotherapy.

开始日期2022-07-29

申办/合作机构

Race Oncology Ltd.

[+1]

NCT04989335

/ Recruiting临床2期IIT

An Open-label, Phase II, Two-stage, Study of Bisantrene(Xantrene) in Combination With Fludarabine and Clofarabine as Salvage Therapy for Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

An Open-label, Phase II, Two-stage, Study of Xantrene® (Bisantrene) in combination with Fludarabine and Clofarabine as Salvage Therapy for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML) Lead-in stage: up to 12 (up to 2 cohorts in a 3+3 dose escalation design) Efficacy stage: up to 17 (Simon 2-stage design 9+8)
Study Objectives:
* Confirm safety and tolerability of the combination regimen
* Time to response with combination treatment
* Overall survival
The treatment regimen will comprise daily IV infusion of Fludarabine (Flu), Clofarabine (Clo) and Bisantrene (Xan) administered via central venous line and controlled-rate infusion pump with a 1-hour break between each agent infusion, amounting to a total of 6 hours for each daily FluCloXan treatment in the following sequence:
* First, infusion over 60 minutes of Fludarabine (Flu) at 10 mg/m2
* Followed by infusion of Clofarabine (Clo) at 30 mg/m2 over 60 minutes
* Followed by infusion of Bisantrene (Xan) at 250 mg/m2 over 2 hours. One cycle will comprise daily IV infusion of the combination treatment course for 4 or 5 consecutive days and rest period to between Day 30 and Day 42, based on patient performance and disease status.

开始日期2021-08-02

申办/合作机构

Sheba Medical Center

[+1]

100 项与比生群二盐酸盐相关的临床结果

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100 项与比生群二盐酸盐相关的转化医学

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100 项与比生群二盐酸盐相关的专利（医药）

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项与比生群二盐酸盐相关的文献（医药）

2025-12-01·JOURNAL OF CLINICAL IMMUNOLOGY

Identification of Potential Therapeutic Agents for Type I Interferonopathy Using iPSC-Based Disease Modeling

Article

作者: Fujio, Keishi ; Taniguchi, Hideki ; Otsu, Makoto ; Natsumoto, Bunki ; Shoda, Hirofumi ; Tsuji, Motonori ; Yamamoto, Kazuhiko

Abstract:

Purpose:

Type I interferonopathy encompasses disorders marked by systemic inflammation and neurological involvement, arising from genetic mutations that result in the upregulation of type I IFN signaling through various mechanisms. Currently, therapeutic options are limited, and no standard therapy exists. This study aims to develop a strategy for identifying new therapeutic targets for type I interferonopathy using induced pluripotent stem cells (iPSCs).

Methods:

The IFIH1 R779H variant was introduced into iPSCs through genome editing. RNA sequencing of iPSC-derived dendritic cells (DCs) was performed, and differentially expressed genes (DEGs) were identified. IFN-α secretion, reactive oxygen species (ROS), and mitochondrial oxygen consumption rate (OCR) were analyzed in iPSC-derived DCs. An in silico prediction of compounds binding to the OAS-like domain was conducted. Candidate compounds were evaluated for their ability to inhibit IFN secretion from IFIH1 R779H-mutated iPSC-derived DCs.

Results:

Transcriptome analysis indicated upregulation of the IFN-related and metabolic pathways. IFIH1 R779H-mutated iPSC-derived DCs exhibited increased OCR and ROS generation, and blocking mitochondrial metabolism significantly reduced excessive IFN-α secretion. Among the DEGs, PML was upregulated, and targeting this gene with arsenic trioxide (ATO), a PML antagonist, suppressed IFN-α secretion from IFIH1 R779H-mutated iPSC-derived DCs. Additionally, bisantrene, phthalylsulfathiazole and ganaplacide were predicted to bind to the RNA binding groove of OAS-like domain of human OASL in silico, effectively inhibiting IFN-α secretion from IFIH1 R779H-mutated DCs.

Conclusion:

Our iPSC-based disease modeling and drug investigation approach provides a robust platform for validating the efficacy and toxicity of candidate therapeutic agents for rare and intractable human diseases such as type I interferonopathy.

Graphical Abstract:

2025-10-01·BRITISH JOURNAL OF HAEMATOLOGY

Bisantrene in combination with fludarabine and clofarabine as salvage therapy for adult patients with refractory or relapsed acute myeloid leukaemia (AML)—An open‐label, phase I/II study

Article

作者: Danylesko, Ivetta ; Andersson, Borje S. ; Yerushalmi, Ronit ; Amitai, Irina ; Avigdor, Abraham ; Nagler, Arnon ; Shimoni, Avichai ; Kedmi, Meirav ; Shem‐Tov, Noga

Summary:

Bisantrene (Bis), an anthracene derivative with topoisomerase‐II inhibitory activity and low cardiotoxicity, may enhance its efficacy when combined with nucleoside analogues such as clofarabine (Clo) and fludarabine (Flu) in preclinical acute myeloid leukaemia (AML) studies. We conducted a phase I/II open‐label study (NCT04989335) to evaluate the safety and efficacy of Bis/Clo/Flu in relapsed/refractory AML. Twenty‐one patients (median age: 47 years, 55% female) received Flu (10 mg/m2), Clo (30 mg/m2) and Bis (250 mg/m2) intravenously for 4 days. Sixteen had relapsed post‐allogeneic stem cell transplantation, and six had extramedullary disease (EMD). Liver toxicity occurred in 10 patients but resolved. No significant cardiac toxicity was observed. Efficacy was assessable in 15 patients, while in six patients, it could not be evaluated due to early non‐relapse mortality occurring within 30 days of treatment initiation, before the first post‐treatment assessment. Six of the 15 patients responded: five achieved complete remission, and one with EMD achieved a partial remission, yielding a 40% response rate. Responses were transient, but six patients, including four undergoing second allo‐HSCTs, proceeded to allo‐HSCT within 1–3 months post‐treatment. The Bis/Clo/Flu regimen demonstrated a tolerable safety profile and potential as a bridging therapy in high‐risk, heavily pretreated AML.

2022-06-07·Leukemia & lymphoma

Enhanced cytotoxicity of bisantrene when combined with venetoclax, panobinostat, decitabine and olaparib in acute myeloid leukemia cells

Article

作者: Andersson, Borje S. ; Nieto, Yago ; Popat, Uday ; Murray, David ; Valdez, Benigno C. ; Yuan, Bin

Bisantrene (Bis), a topoisomerase-II inhibitor, is less cardiotoxic than the current anthracyclines. Its synergistic cytotoxicity with newly developed antineoplastic drugs has not been reported. We demonstrated the synergism of [Bis + ABT199/venetoclax] in combination with panobinostat (Pano), decitabine (DAC), or olaparib (Ola), known inhibitors of BCL2, histone deacetylase, DNA methyltransferase, and poly(ADP-ribose) polymerase, respectively, in AML cells. [Bis + ABT199] with Pano, DAC, or Ola synergistically inhibited cell proliferation with combination indices of 0.25-0.6, 0.2-0.35, and 0.2-0.4 (at 50% inhibition of proliferation), respectively. Increased γ-H2AX suggests enhanced DNA damage; cleavages of Caspase 3 and PARP1, DNA fragmentation, increased ROS, and decreased MMP indicate potent apoptosis activation. Similar results were observed using mononuclear cells from leukemia patients but not from healthy donors. The SAPK/JNK signaling pathway was strongly activated by the combination treatments, whereas the PI3K/mTOR and Wnt/β-catenin pro-survival pathways were inhibited. These drug combinations may be used in cytoreductive clinical trials for AML patients.

项与比生群二盐酸盐相关的新闻（医药）

2023-08-09

·美通社

Race提供2023年8月战略更新

悉尼 2023年8月10日 /美通社/ -- Race Oncology Limited（以下简称"Race"）欣然提供战略更新，包括修订企业战略，旨在优化现有资源的利用，同时推动bisantrene的商业合作与协作潜力。不断发展的企业战略 Race的新战略旨在最大程度发挥bisantrene的内在价值：抗癌 +心脏保护 Race的核心重点是影响癌症疗效并应对化疗心脏毒性的挑战。研究将利用bisantrene在具有高度未满足需求的两种癌症患者群体转移性乳腺癌(mBC)和急性髓系白血病(AML)中的独特机制，为未来一系列适应症铺平了道路。转移性乳腺癌 (mBC) mBC患者将从一种可以同时提供抗癌和心脏保护的治疗方法中大大受益，该方法改善了安全性，可以提供更多剂量。 mBC已被确定为bisantrene的主要适应症，这为Race提供了机会来满足这一明确的高度未满足的患者需求。美国每年约有36000名mBC患者，商机巨大。 Race计划将bisantrene RC220与mBC中使用最广泛的化疗药物蒽环类抗癌药物阿霉素联合进行1/2期临床试验。一旦RC220获得GMP（药品生产质量管理规范），并完成毒理学研究、伦理审查和监管批准，将启动该试验。预计试验将于2024年第三季度开始。急性髓系白血病 (AML) AML计划仍然是Race战略的关键部分，因为目前尚需要一种新的治疗方法来改善现有的癌症治疗选择，同时减少对每年不适合其他疗法的约16,000名美国AML患者的毒性影响。 Race计划将bisantrene纳入1b/2a期临床试验，在该试验中将与口服地西他滨/西屈嘧啶联合使用，进行剂量递增研究，随后再与标准治疗进行三联组合。初始阶段将从最初的RC110（中心静脉给药）制剂过渡到RC220。该试验计划于2023年第四季度末开始，并在2024年进入从RC110到RC220的过渡。 Race认为，AML计划为建立早期商业合作提供了重要机会。发现我们的发现项目旨在进一步阐明bisantrene的心脏保护作用机制，以及City of Hope的发现，即bisantrene是最强效的FTO抑制剂。这一发现提示可以选择性地向FTO过度表达的患者进行靶向治疗。这个发现项目将会：继续深入研究bisantrene独特的作用机制，以实现在与蒽环类药物联合使用时减少心脏毒性及相关心脏保护的效果帮助明确蒽环类药物与阿霉素等蒽环类药物之间的个体临床优势通过City of Hope联盟加强对FTO的探索与莫纳什大学进一步开展FTO抑制剂发现项目深入了解m6A通路内的作用机制开发可在临床中使用的生物标志物检测方法新 bisantrene 在这个项目下进行的活动旨在加强bisantrene的知识产权，开发新一代bisantrene，以改善患者的疗效和体验。该项目将：在RC110的基础上进行扩展和利用，将 RC220纳入临床开发新一代 bisantrene ，扩大治疗适应症，加强知识产权，增强合作选择，从而有望延长bisantrene的整体生命周期。更多后续适应症 Race对mBC和AML的关注使其将其他具有前景数据的研究适应症归类为"后续适应症"。这些疾病领域包括黑色素瘤、软组织肉瘤、肾细胞小细胞癌和肺癌。商业化战略 Race已做好商业化准备，将参与国际生物制药对话，为合作机会创造条件。Race相信其临床计划增强并提供了独特的商机，现在可以由适当的市场内制药公司实现。 Race保留了充足的现金储备。AML 1b /2a期研究和承诺的临床前项目已获得充分资金支持。Race正在研究各种资金筹集途径，为预计将于2024年末开始的mBC研究提供资金。战略更新和Strategy Deck可在此下载。

2023-07-12

·美通社

Race与Ardena签署按GMP规范生产RC220的协议

Race Oncology与全球领先的合同开发和制造组织Ardena签署协议，后者成为按GMP规范生产bistanrene旗舰注射剂 RC220的第二合作伙伴 Ardena在为各临床开发阶段提供无菌注射剂产品方面拥有悠久的历史此次合作增强了 Race现有的生产计划，Ardena也成为欧盟临床研究所需的欧盟合规产品的主要供应商，为美国和澳大利亚的临床项目提供后备供应来源。悉尼 2023年7月13日 /美通社/ -- Race Oncology Limited（以下简称"Race"）欣然宣布，公司已与全球领先的合同开发和制造组织（CDMO）Ardena Holding NV（以下简称"Ardena"）签署协议。根据该协议，Ardena将为Race的bisantrene旗舰静脉注射剂RC220提供符合药品生产质量管理规范（cGMP）的额外生产能力。 Ardena是一家综合性CDMO，为生物制药公司提供横跨整个药物开发生命周期的服务。该公司在为各临床开发阶段提供无菌注射剂产品方面拥有悠久的历史。此次合作增强了Race现有的生产计划，Ardena也成为欧盟临床研究所需的、符合欧盟相关标准的RC220的主要供应商，为美国和澳大利亚的临床项目提供了后备供应来源。首席执行官兼董事总经理 Damian Clarke-Bruce 表示： "我们很高兴欢迎 Ardena成为我们的生产合作伙伴，他们将增强我们现有的合同制造能力。Ardena在欧洲的地位确保我们能够轻松获得欧洲临床试验所需的RC220产品，他们也成为符合FDA标准的医药级产品的第二个供应商。" 根据该合同，最初的开发预算约为100万美元。Ardena预计将为Race提供首批符合欧盟和国际GMP标准的产品，并在2023年底前完成目标。未来几个月内将开展技术转让工作，正式启动该项目。与Ardena签署的协议初始期限为5年，之后将自动延长一年，除非根据协议条款提前终止。

并购临床研究

2023-07-12

·BioSpace

Race executes agreement with Ardena for GMP manufacturing of RC220

Race Oncology executes agreement with leading global contract development and manufacturing organisation, Ardena as additional partner for GMP manufacturing of flagship RC220 bistanrene formulation Ardena has a long track record of providing sterile injectable products for all stages of clinical development Partnership strengthens the existing manufacturing programs by serving as a primary source for EU compliant supplies required for EU clinical studies, while also providing a backup source for US and Australian clinical programs. SYDNEY, July 12, 2023 /PRNewswire/ -- Race Oncology Limited ("Race") is pleased to announce that it has signed an agreement with leading global contract development and manufacturing organisation (CDMO), Ardena Holding NV (Ardena) to provide additional Good Manufacturing Practice (cGMP)-standard manufacturing capability for Race's flagship intravenous (IV) formulation of bisantrene, RC220. Ardena is a fully integrated CDMO which assists biopharma companies with services spanning the drug development life cycle. The company has a long track record of providing sterile injectable products for all stages of clinical development. The partnership strengthens Race's existing manufacturing programs by serving as a primary source for EU compliant supplies of RC220 required for EU clinical studies. It also provides a backup source for US and Australian clinical programs. CEO and Managing Director, Damian Clarke-Bruce commented: "We are pleased to welcome Ardena as a manufacturing partner, adding to our existing contracted manufacturing capability. Ardena's position in Europe ensures ease of access to RC220 product for our European clinical trials and adds a second source of FDA-compliant pharmaceutical grade product." The initial development budget contracted is approximately USD $1m. Ardena is expected to provide Race's first EU and international compliant GMP supplies with goal of completion being by the end of 2023. Technology transfer to formally commence the program will occur in the coming months. The agreement with Ardena is for an initial period of 5 years and shall then be automatically extended for successive one year periods unless terminated earlier in accordance with the terms of the agreement. Company Codes: Australia:RAC

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100 项与比生群二盐酸盐相关的药物交易

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适应症	国家/地区	公司	日期
急性髓性白血病	法国	Wyeth Pharmaceuticals LLC	1990-01-01

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适应症	最高研发状态	国家/地区	公司	日期
复发性急性髓细胞白血病	临床2期	以色列	Race Oncology Ltd.	2021-08-02
造血干细胞移植	临床2期	以色列	Race Oncology Ltd.	2019-07-18
难治性急性髓细胞白血病	临床2期	以色列	Race Oncology Ltd.	2019-07-18
晚期恶性实体瘤	临床1期	澳大利亚	Race Oncology Ltd.	2025-04-02
晚期恶性实体瘤	临床1期	中国香港	Race Oncology Ltd.	2025-04-02
慢性粒单核细胞白血病	临床1期	澳大利亚	Race Oncology Ltd.	2022-07-29
髓外浆细胞瘤	临床1期	澳大利亚	Race Oncology Ltd.	2022-07-29
高危骨髓增生异常综合征	临床1期	澳大利亚	Race Oncology Ltd.	2022-07-29
髓系肉瘤	临床1期	澳大利亚	Race Oncology Ltd.	2022-07-29
复发性急性白血病	临床1期	澳大利亚	Race Oncology Ltd.	2022-07-29

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03820908 (Pubmed \| Eur J Haematol) 人工标引	临床2期	急性髓性白血病	10	bisantrene	衊襯淵醖艱糧簾積糧襯(襯顧壓餘鹹餘廠艱網淵) = 網鏇餘齋膚觸選廠膚積鹽窪積獵糧繭糧鹹艱膚 (簾範夢觸鬱憲淵遞製鹽 )	积极	2021-02-01