Bleximenib, an investigational selective menin inhibitor, shows potential as combination therapy for the treatment of relapsed or refractory AML and newly diagnosed, intensive chemo-ineligible AML

Bleximenib，一种研究性的选择性menin抑制剂，作为联合疗法在治疗复发或难治性急性髓系白血病（AML）以及新诊断但无法接受高强度化疗的AML中显示出潜力。

Phase 1b data show low rate of differentiation syndrome and no cardiac safety signal of QTc prolongation

第1b阶段数据显示分化综合征发生率低，且无QTc延长的心脏安全性信号。

MILAN

米兰

,

，

June 12, 2025

2025年6月12日

/PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) today announced new Phase 1b data showing encouraging antileukemic activity and a promising safety profile for bleximenib (JNJ-75276617) in combination with venetoclax and azacitidine (VEN + AZA) for the treatment of acute myeloid leukemia (AML) harboring .

/PRNewswire/ -- 约翰逊公司（纽约证券交易所代码：JNJ）今天宣布了新的1b期数据，显示布雷西米尼（JNJ-75276617）与维奈托克和阿扎胞苷（VEN + AZA）联合治疗携带特定基因突变的急性髓系白血病（AML）具有令人鼓舞的抗白血病活性和良好的安全性。

KMT2A

KMT2A

gene rearrangements (

基因重排 (

KMT2Ar

KMT2Ar

) or

) 或

NPM1

NPM1

gene mutations (

基因突变 (

NPM1m

NPM1m

). The study evaluated patients with newly diagnosed, intensive chemo-ineligible AML and relapsed or refractory AML.

）。该研究评估了新诊断的、无法接受强化化疗的急性髓系白血病患者以及复发或难治性急性髓系白血病患者。

1

1

The results were featured in an oral presentation at the

结果在一场口头报告中被展示，

2025 European Hematology Association (EHA) Congress

2025年欧洲血液学协会（EHA）大会

(

(

S137

S137

).

）。

Even though AML is the most common type of acute leukemia in adults, it has the lowest survival rate and is associated with poor patient outcomes, despite treatment advances to date – especially for patients with

尽管AML是成人中最常见的急性白血病类型，但其生存率最低，且患者预后较差，尽管迄今为止治疗已有所进展——尤其是对于患有该病的患者来说。

KMT2Ar

KMT2Ar

and

和

NPM1m.

NPM1m。

2,3,4

2，3，4

'AML encompasses a spectrum of genetically diverse cancers affecting the bone marrow and blood, which progress rapidly, making it an extremely challenging cancer to treat,' said Andrew M. Wei*, MBBS, PhD, Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Walter and Eliza Hall Institute of Medical Research and University of Melbourne, Australia.

“急性髓系白血病（AML）包含一系列影响骨髓和血液的基因多样性癌症，其进展迅速，是一种极难治疗的癌症，”澳大利亚彼得·麦卡勒姆癌症中心、皇家墨尔本医院、沃尔特和伊丽莎·霍尔医学研究所及墨尔本大学的Andrew M. Wei博士表示。

'These data highlight the potential of this targeted therapy in combination with VEN + AZA for patients with newly diagnosed AML who are ineligible for intensive chemotherapy or with disease that has relapsed after prior therapy.'.

“这些数据突显了这种靶向治疗与VEN + AZA联合用于新诊断的不适合强化化疗或既往治疗后复发的AML患者的潜力。”

The Phase 1b dose-finding study (

第1b阶段剂量探索研究 (

NCT05453903

NCT05453903

) evaluated 125 patients with relapsed or refractory AML and newly diagnosed, intensive chemo-ineligible AML who harbored

）评估了125名复发或难治性AML患者以及新诊断出的、无法接受高强度化疗的AML患者，这些患者携带

KMT2Ar

KMT2Ar

(n=52) or

(n=52) 或

NPM1m

NPM1m

(n=73). Bleximenib in combination with VEN + AZA was evaluated across multiple dose levels without step-up dosing. Of the 85 relapsed or refractory patients, 36 percent received one, 42 percent received two and 12 percent received three lines of prior treatment; 47 percent had previously been treated with venetoclax..

(n=73)。Bleximenib联合VEN + AZA在多个剂量水平进行了评估，未采用逐步加量给药。在85名复发或难治性患者中，36%接受了一线治疗，42%接受了二线治疗，12%接受了三线治疗；47%之前曾接受过维奈托克治疗。

1

1

The bleximenib data at 100 mg twice a day in combination with VEN + AZA showed higher efficacy and a similar safety profile in comparison to other dose levels. At the recommended Phase 2 dose (RP2D), patients with relapsed or refractory AML achieved an overall response rate (ORR) of 82 percent and a composite complete response (cCR) rate of 59 percent..

每天两次100毫克的布雷西米尼与VEN + AZA联合使用时显示出更高的疗效和与其他剂量水平相似的安全性。在推荐的二期剂量（RP2D）下，复发或难治性急性髓系白血病患者达到了82%的总缓解率（ORR）和59%的综合完全缓解率（cCR）。

1

1

The newly diagnosed, intensive chemo-ineligible patient population showed an ORR of 90 percent and a cCR rate of 75 percent.

新诊断的、无法接受强化疗的患者群体显示出90%的总缓解率（ORR）和75%的完全临床缓解率（cCR）。

1

1

Safety analysis of the study population showed a profile comparable among dose groups, genetic subtypes and disease settings. At the RP2D in combination with VEN+AZA, differentiation syndrome events were reported in two of 49 patients (4 percent). Bleximenib safety data continued to support a lack of QTc prolongation signal, with no events of Grade 3 or higher and only three Grade 1 events (6 percent) at the RP2D..

研究人群的安全性分析显示，各剂量组、基因亚型和疾病环境中的表现相似。在RP2D剂量下与VEN+AZA联合使用时，49名患者中有两名（4%）报告了分化综合征事件。Bleximenib的安全数据继续支持无QTc延长信号，没有发生3级或更高级别的事件，在RP2D剂量下仅出现三起1级事件（6%）。

1

1

The most common all-grade treatment-emergent adverse events (TEAEs) were nausea (65 percent), thrombocytopenia (61 percent), neutropenia (59 percent) and anemia (49 percent).

最常见的各级治疗中出现的不良事件（TEAEs）为恶心（65%）、血小板减少症（61%）、中性粒细胞减少症（59%）和贫血（49%）。

1

1

The most common Grade 3 or higher TEAEs were thrombocytopenia (59 percent), neutropenia (59 percent), and anemia (49 percent).

最常见的 3 级或更高级别的 TEAE 是血小板减少症 (59%)、中性粒细胞减少症 (59%) 和贫血 (49%)。

1

1

'Building on our heritage of leadership and innovation in hematologic malignancies, we are committed to delivering transformative treatment options that address the significant unmet needs of patients with acute myeloid leukemia,' said Jeffrey Infante, M.D., Vice President of Early Clinical Development and Translational Research at Johnson & Johnson Innovative Medicine.

“基于我们在血液系统恶性肿瘤领域的领导力和创新传统的基础，我们致力于提供能够满足急性髓系白血病患者重大未满足需求的变革性治疗方案，”强生创新药物公司早期临床开发与转化研究副总裁Jeffrey Infante博士表示。

'We continue to explore the potential of this compound as a monotherapy and in combination with standard of care regimens in additional Phase 2 and 3 studies, which are currently enrolling patients.'.

“我们继续在更多的二期和三期研究中探索这种化合物作为单一疗法以及与标准治疗方案联合使用的潜力，这些研究目前正在招募患者。”

About Phase 1b Bleximenib Combination Dosing Study

关于Bleximenib联合剂量研究的第1b阶段

This bleximenib combination trial (NCT05453903) is an ongoing Phase 1b open-label, non-randomized sequential assignment multicenter study to determine the recommended Phase 2 dose (RP2D) and further evaluate the safety and tolerability of bleximenib in combination with VEN + AZA in approximately 200 patients with either newly diagnosed or relapsed/refractory acute myeloid leukemia harboring .

这项布雷西米尼联合试验（NCT05453903）是一项正在进行的Ib期开放标签、非随机顺序分配的多中心研究，旨在确定推荐的II期剂量（RP2D），并进一步评估布雷西米尼联合VEN + AZA在约200名新诊断或复发/难治性急性髓系白血病患者中的安全性和耐受性。

KMT2A

KMT2A

or

或

NPM1

NPM1

alterations.

更改。

Patients received VEN + AZA in combination with oral bleximenib twice daily at 15–150 mg (relapsed/refractory) or 30–100 mg (newly diagnosed) over a 28-day cycle and during count recovery. Bleximenib was started on day 4 without the need for step-up dosing. Primary outcome measures included adverse events and dose-limiting toxicity.

患者在接受 VEN + AZA 联合治疗的同时，口服 bleximenib，每日两次，剂量为 15-150 mg（复发/难治性患者）或 30-100 mg（新诊断患者），持续 28 天一个周期，并在血细胞计数恢复期间继续服用。Bleximenib 从第 4 天开始给药，无需逐步增加剂量。主要结局指标包括不良事件和剂量限制性毒性。

Secondary efficacy measures included depletion of leukemic blasts, percentage of patients achieving complete response (CR), and percentage of patients who achieve overall response..

次要疗效指标包括白血病原始细胞的减少、达到完全缓解（CR）的患者百分比以及达到总体缓解的患者百分比。

About Bleximenib (JNJ-75276617)

关于Bleximenib（JNJ-75276617）

Bleximenib is an investigational oral menin inhibitor being evaluated for the treatment of patients with newly diagnosed and relapsed or refractory AML. It targets a key oncogenic interaction between menin and

Bleximenib 是一种正在研究中的口服 menin 抑制剂，正被评估用于治疗新诊断及复发或难治性 AML 患者。它针对 menin 与关键致癌相互作用之间的关系。

KMT2A

KMT2A

fusion proteins, disrupting a pathway that drives leukemic cell growth in patients with

融合蛋白，破坏了驱动白血病患者细胞生长的途径

KMT2Ar

KMT2Ar

or

或

NPM1m

NPM1m

mutations.

突变。

It is currently being investigated in Phase 1, 2, and 3 trials, both as a monotherapy and in combination with AML-directed therapies to further explore its potential in both relapsed or refractory and newly diagnosed AML populations.

目前，它正在进行 I、II 和 III 期试验，既作为单一疗法，也与针对急性髓系白血病（AML）的疗法联合使用，以进一步探索其在复发或难治性以及新诊断的急性髓系白血病人群中的潜力。

About Acute Myeloid Leukemia (AML)

关于急性髓系白血病 (AML)

Acute myeloid leukemia is an aggressive, fast-growing blood cancer that originates in the bone marrow and is marked by the uncontrolled proliferation of immature white blood cells known as myeloblasts.

急性髓系白血病是一种侵袭性极强、快速生长的血液癌症，起源于骨髓，其特征是未成熟白细胞（称为髓母细胞）的失控增殖。

2, 5

2, 5

These malignant cells crowd out healthy blood-forming cells, leading to complications such as anemia, infections and bleeding.

这些恶性细胞会排挤健康的造血细胞，导致贫血、感染和出血等并发症。

6

6

Acute myeloid leukemia progresses rapidly, often requiring immediate treatment after diagnosis.

急性髓系白血病进展迅速，通常在诊断后需要立即治疗。

5

5

It is the most common type of acute leukemia in adults, with a median age of diagnosis around 70 years.

它是成人中最常见的急性白血病类型，诊断的中位年龄大约为70岁。

2

2

Despite treatment advances, acute myeloid leukemia remains associated with poor patient outcomes, particularly in older adults or those with high-risk genetic profiles.

尽管治疗有所进展，急性髓系白血病仍然与患者预后不良相关，特别是在老年人或具有高风险遗传特征的人群中。

7

7

The five-year survival rate remains the lowest among leukemias, with outcomes especially poor in patients with

五年的生存率在白血病中仍然是最低的，尤其是患者的结果较差。

KMT2Ar

KMT2Ar

or

或

NPM1m

NPM1m

where relapse/refractory disease survival can be as short as 2 to 3 months after a second relapse – highlighting a significant unmet medical need.

复发/难治性疾病的生存期在第二次复发后可能短至 2 到 3 个月——突显了未满足的重大医疗需求。

7

7

About Johnson & Johnson

关于强生公司

At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.

在强生，我们相信健康就是一切。我们在医疗保健创新方面的实力使我们能够构建一个世界，在这个世界中，复杂疾病得以预防、治疗和治愈，治疗方法更加智能且侵入性更小，解决方案也更加个性化。凭借我们在创新药物和医疗技术方面的专业知识，我们有能力在当今整个医疗保健解决方案领域进行创新，提供明日的突破性成果，并对人类健康产生深远影响。

Learn more at .

了解更多，请访问。

https://www.jnj.com/

https://www.jnj.com/

or at

或在

https://www.innovativemedicine.jnj.com.

https://www.innovativemedicine.jnj.com.

Follow us at

关注我们

@JanssenUS

@JanssenUS

and

和

@JNJInnovMed

@JNJInnovMed

. Janssen Research & Development, LLC, Janssen Biotech, Inc., and Janssen Global Services, LLC are Johnson & Johnson companies.

杨森研发有限责任公司、杨森生物科技公司和杨森全球服务有限责任公司均为强生公司旗下企业。

Cautions Concerning Forward-Looking Statements

关于前瞻性陈述的注意事项

This press release contains 'forward-looking statements' as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of

本新闻稿包含《1995年私人证券诉讼改革法案》中定义的关于产品开发以及潜在益处和治疗影响的“前瞻性声明”。

bleximenib (JNJ-75276617)

布雷西米尼（JNJ-75276617）

. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson.

读者被提醒不要依赖这些前瞻性陈述。这些陈述是基于对未来事件的当前预期。如果基本假设被证明不准确，或已知或未知的风险或不确定性成为现实，实际结果可能与强生公司的预期和预测大相径庭。

Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment.

风险和不确定性包括但不限于：产品研究和开发中固有的挑战和不确定性，包括临床成功的不确定性和获得监管批准的不确定性；商业成功的不确定性；生产困难和延误；竞争，包括技术进步、竞争对手推出的新产品和获得的专利；专利面临的挑战；产品功效或安全问题导致的产品召回或监管行动；医疗保健产品和服务购买者的行为和支出模式的变化；适用法律法规的变更，包括全球医疗改革；以及控制医疗成本的趋势。

A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's most recent Annual Report on Form 10-K, including in the sections captioned 'Cautionary Note Regarding Forward-Looking Statements' and 'Item 1A. Risk Factors,' and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission.

这些风险、不确定性和其他因素的更多列表和描述，请参见强生公司最近的年度报告 Form 10-K，包括标题为“关于前瞻性陈述的警示声明”和“项目1A. 风险因素”的部分，以及强生公司随后的季度报告 Form 10-Q 和其他提交给证券交易委员会的文件。

Copies of these filings are available online at .

这些文件的副本可在线获取，网址为 。

www.sec.gov

www.sec.gov

,

，

www.jnj.com

www.jnj.com

or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.

或应Johnson & Johnson的要求。Johnson & Johnson不承担因新信息或未来事件或发展而更新任何前瞻性声明的义务。

Footnotes:

脚注：

*

*

Andrew M. Wei, MBBS, PhD, Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Walter and Eliza Hall Institute of Medical Research and University of Melbourne, Australia has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.

澳大利亚彼得·麦卡勒姆癌症中心、皇家墨尔本医院、沃尔特和伊丽莎·霍尔医学研究所及墨尔本大学的魏安德鲁博士（MBBS, PhD）曾为强生公司提供咨询、顾问和演讲服务；他未因任何媒体工作获得报酬。

1

1

Wei, A.H., et al. RP2D Determination of Bleximenib in Combination with VEN+AZA: Phase 1b study in ND & R/R AML with KMT2A/NPM1 Alterations. 2025 EHA Annual Congress – European Hematology Association. June 2025. Available at:

魏,A.H.,等。Bleximenib联合VEN+AZA的RP2D测定：在伴有KMT2A/NPM1突变的初诊和复发/难治性AML中的1b期研究。2025年欧洲血液学协会年度大会（EHA）。2025年6月。可见于：

https://library.ehaweb.org/eha/2025/eha2025-congress/4159214/

https://library.ehaweb.org/eha/2025/eha2025-congress/4159214/

. Accessed June 2025.

。访问时间：2025年6月。

2

2

The Leukemia & Lymphoma Society. Facts 2022–2023: Updated data on blood cancers.

白血病和淋巴瘤协会。2022-2023年事实：血液癌症的更新数据。

https://www.lls.org/sites/default/files/2023-08/PS80_Facts_2022_2023.pdf

https://www.lls.org/sites/default/files/2023-08/PS80_Facts_2022_2023.pdf

. Accessed June 2025.

。访问时间：2025年6月。

3

3

Cancer Research UK. Survival for acute myeloid leukaemia (AML).

英国癌症研究中心。急性髓系白血病（AML）的生存率。

https://www.cancerresearchuk.org/about-cancer/acute-myeloid-leukaemia-aml/survival

https://www.cancerresearchuk.org/about-cancer/急性髓系白血病-aml/生存率

. Accessed June 2025.

访问时间：2025年6月。

4

4

Khan, A.M., et al. Comprehensive age–stratified impact of NPM1 mutation in acute myeloid leukemia.

汗，A.M.，等。NPM1突变在急性髓系白血病中的综合年龄分层影响。

Blood.

血液。

2022;140(Supplement 1):1433–1434. American Society of Hematology (ASH) Annual Meeting Abstract. Available at:

2022;140(补充1):1433–1434. 美国血液学会 (ASH) 年会摘要。可见于:

https://doi.org/10.1182/blood-2022-165696

https://doi.org/10.1182/blood-2022-165696

. Accessed June 2025.

访问日期：2025年6月。

5

5

MD Anderson Cancer Center. Acute myeloid leukemia.

MD安德森癌症中心。急性髓系白血病。

https://www.mdanderson.org/cancer-types/acute-myeloid-leukemia.html

https://www.mdanderson.org/cancer-types/急性髓系白血病.html

. Accessed June 2025.

。访问时间：2025年6月。

6

6

American Cancer Society. Signs and symptoms of acute myeloid leukemia (AML).

美国癌症协会。急性髓系白血病（AML）的体征和症状。

https://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/signs-symptoms.html.

https://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/signs-symptoms.html

Accessed June 2025.

访问时间：2025年6月。

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7

Shimony, S., Stahl, M., & Stone, R.M. Acute myeloid leukemia: 2023 update on diagnosis, risk–stratification, and management.

Shimony, S., Stahl, M., & Stone, R.M. 急性髓系白血病：2023年关于诊断、风险分层和管理的更新。

American Journal of Hematology.

美国血液学杂志。

2023;98(3):502–526.

2023；98（3）：502–526。

https://doi.org/10.1002/ajh.26822

https://doi.org/10.1002/ajh.26822

. Accessed June 2025.

。引用日期：2025年6月。

Media contact:

媒体联系人：

Oncology Media Relations

肿瘤学媒体关系

Oncology_media_relations@its.jnj.com

肿瘤学媒体关系@its.jnj.com

Investor contact:

投资者联系方式：

Lauren Johnson

劳伦·约翰逊

investor-relations@its.jnj.com

投资者关系@its.jnj.com

U.S. medical inquiries:

美国医学咨询：

+1 800 526-7736

+1 800 526-7736

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查看原始内容以下载多媒体：

https://www.prnewswire.com/news-releases/new-results-for-johnson--johnsons-bleximenib-demonstrate-promising-antileukemic-activity-in-combination-with-venetoclax-and-azacitidine-for-acute-myeloid-leukemia-302480190.html

https://www.prnewswire.com/news-releases/new-results-for-johnson--johnsons-bleximenib-demonstrate-promising-antileukemic-activity-in-combination-with-venetoclax-and-azacitidine-for-acute-myeloid-leukemia-302480190.html

SOURCE Johnson & Johnson

来源：强生公司