Decitabine

Oncology R&D News Combination therapy has potential to be an all-oral, fixed-duration regimen for previously untreated patients with CLL Application is supported by data from the Phase 3 AMPLIFY trial that showed statistically significant improvement in progression-free survival vs chemoimmunotherapy Regimen offers an opportunity for patients to take time off treatment, an important step toward improved disease management NORTH CHICAGO, Ill., July 29, 2025 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for the fixed-duration, all-oral combination regimen of VENCLEXTA® (venetoclax) and acalabrutinib in previously untreated patients with CLL, offering CLL patients another VENCLEXTA combination regimen with the potential for time-limited treatment. The submission is based on the positive results from the Phase 3 AMPLIFY trial.1 The combination regimen of VENCLEXTA and acalabrutinib improved progression-free survival (PFS) compared to standard chemoimmunotherapy in previously untreated patients with CLL.2 "This FDA submission marks a milestone for CLL treatment with the potential approval for the first oral combination regimen of VENCLEXTA and acalabrutinib for previously untreated patients with chronic blood cancer. This new fixed-treatment duration approach could allow patients the opportunity for time off treatment, if approved, and be potentially practice-changing in frontline CLL care," said Svetlana Kobina, vice president, global medical affairs, oncology, AbbVie. About the AMPLIFY Study AMPLIFY is an AstraZeneca-sponsored, global, multi-center Phase 3 trial evaluating VENCLEXTA plus acalabrutinib alone or combined with obinutuzumab versus chemoimmunotherapy in patients with previously untreated CLL without del(17p) or TP53 mutation.1 Data presented at the 2024 American Society of Hematology Annual Meeting showed that the fixed-duration combination regimen of VENCLEXTA and acalabrutinib reduced the risk of disease progression or death by 35% vs chemoimmunotherapy (HR 0.65; 95% CI: 0.49-0.87; p=0.004). The safety profile of the VENCLEXTA and acalabrutinib combination regimen is consistent with the known safety profile of each individual therapy alone. The most common adverse events in any grade were neutropenia, hemorrhage, and COVID-19 in patients administered VENCLEXTA plus acalabrutinib. The most frequent Grade 3 or higher adverse event was neutropenia seen in 26.8% of patients. Among events of clinical interest, low rates of tumor lysis syndrome were observed with events of any grade seen in 0.3% of patients treated with VENCLEXTA plus acalabrutinib compared to 3.1% for patients treated with chemoimmunotherapy. No new safety signals were observed in the AMPLIFY study.2 About VENCLEXTA® (venetoclax) VENCLEXTA (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLEXTA targets the BCL-2 protein and works to help restore the process of apoptosis. VENCLEXTA is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers. Venetoclax is approved in more than 80 countries, including the U.S. VENCLEXTA® (venetoclax) U.S. Uses and Important Safety Information3 Uses VENCLEXTA is a prescription medicine used: to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly diagnosed acute myeloid leukemia (AML) who: ‒ are 75 years of age or older, or ‒ have other medical conditions that prevent the use of standard chemotherapy. It is not known if VENCLEXTA is safe and effective in children. Important Safety Information What is the most important information I should know about VENCLEXTA? VENCLEXTA can cause serious side effects, including: Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your healthcare provider will do tests to check your risk of getting TLS before you start taking VENCLEXTA. You will receive other medicines before starting and during treatment with VENCLEXTA to help reduce your risk of TLS. You may also need to receive intravenous (IV) fluids into your vein. Your healthcare provider will do blood tests to check for TLS when you first start treatment and during treatment with VENCLEXTA. It is important to keep your appointments for blood tests. Tell your healthcare provider right away if you have any symptoms of TLS during treatment with VENCLEXTA, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain. Drink plenty of water during treatment with VENCLEXTA to help reduce your risk of getting TLS. Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased. Your healthcare provider may delay, decrease your dose, or stop treatment with VENCLEXTA if you have side effects. When restarting VENCLEXTA after stopping for 1 week or longer, your healthcare provider may again check for your risk of TLS and change your dose. Who should not take VENCLEXTA? Certain medicines must not be taken when you first start taking VENCLEXTA and while your dose is being slowly increased because of the risk of increased TLS. Tell your healthcare provider about all the medicines you take, including prescription and over-the- counter medicines, vitamins, and herbal supplements. VENCLEXTA and other medicines may affect each other causing serious side effects. Do not start new medicines during treatment with VENCLEXTA without first talking with your healthcare provider. Before taking VENCLEXTA, tell your healthcare provider about all of your medical conditions, including if you: have kidney or liver problems. have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium. have a history of high uric acid levels in your blood or gout. are scheduled to receive a vaccine. You should not receive a "live vaccine" before, during, or after treatment with VENCLEXTA, until your healthcare provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your healthcare provider. These vaccines may not be safe or may not work as well during treatment with VENCLEXTA. are pregnant or plan to become pregnant. VENCLEXTA may harm your unborn baby. If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with VENCLEXTA, and you should use effective birth control during treatment and for 30 days after the last dose of VENCLEXTA. If you become pregnant or think you are pregnant, tell your healthcare provider right away. are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk. Do not breastfeed during treatment with VENCLEXTA and for 1 week after the last dose. What should I avoid while taking VENCLEXTA? You should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood. What are the possible side effects of VENCLEXTA? VENCLEXTA can cause serious side effects, including: Low white blood cell counts (neutropenia). Low white blood cell counts are common with VENCLEXTA, but can also be severe. Your healthcare provider will do blood tests to check your blood counts during treatment with VENCLEXTA and may pause dosing. Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with VENCLEXTA. Your healthcare provider will closely monitor and treat you right away if you have a fever or any signs of infection during treatment with VENCLEXTA. Tell your healthcare provider right away if you have a fever or any signs of an infection during treatment with VENCLEXTA. The most common side effects of VENCLEXTA when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell counts; low platelet counts; low red blood cell counts; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of your arms, legs, hands, and feet. The most common side effects of VENCLEXTA in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure. VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if you have concerns about fertility. These are not all the possible side effects of VENCLEXTA. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. The full U.S. prescribing information, including Medication Guide, for VENCLEXTA can be found here. Globally, prescribing information varies; refer to the individual country product label for complete information. About AbbVie AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas including immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube. About AbbVie in Oncology At AbbVie, we are committed to transforming standards of care for patients living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities and biology interventions, including small molecule therapeutics, antibody-drug conjugates (ADCs), immuno-oncology-based therapeutics, multispecific antibody and in situ CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines. Today, our expansive oncology portfolio comprises approved and investigational treatments for a wide range of blood and solid tumors. We are evaluating more than 20 investigational medicines in multiple clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology. Forward-Looking Statements Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry, the impact of global macroeconomic factors, such as economic downturns or uncertainty, international conflict, trade disputes and tariffs, and other uncertainties and risks associated with global business operations. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2024 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its Quarterly Reports on Form 10-Q and in other documents that AbbVie subsequently files with the Securities and Exchange Commission that update, supplement or supersede such information. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. References: US Media: Matt Skryja Matt.skryja@abbvie.com Investors: Liz Shea Liz.shea@abbvie.com SOURCE AbbVie

点击蓝字关注我们编者按：2025年中国临床肿瘤学会年度进展研讨会（BOC）暨Best of ASCO 2025 China（BOC/BOA）于7月4日至5日在南京盛大召开。此次会议汇聚了国内外肿瘤学领域的顶尖专家，共同回顾并探讨过去一年中国临床肿瘤学的重大进展，并分享刚刚落幕的美国临床肿瘤学会（ASCO）年会的前沿成果。在本次会议中，CSCO白血病专委会主任委员、中国医学科学院血液病医院（中国医学科学院血液学研究所）姜尔烈教授分享了两项急性髓系白血病（AML）领域的突破性研究，并在接受采访时进一步解读了这两项研究的重要意义与临床价值。重磅研究一地西他滨-西达尿苷（DEC-C）联合维奈克拉（VEN）全口服方案用于不适合强化诱导化疗的新诊断急性髓系白血病（AML）患者：来自101例患者的Ⅱ期队列研究结果（摘要号：6504)背景：对于年龄≥75岁且不适合接受诱导化疗的AML患者，BCL-2抑制剂维奈克拉（VEN）联合阿扎胞苷（AZA）已获批准，该批准基于III期VIALE-A临床试验（完全缓解率[CR]为36.7%；中位CR持续时间为17.5个月；中位总生存期[OS]为14.7个月）。然而，患者需每月接受为期7天的阿扎胞苷静脉注射直到疾病进展，这给患者带来了较大负担。此外，多项校正后比较研究显示，阿扎胞苷与地西他滨的临床疗效相似。口服DEC-C（地西他滨35 mg，塞西达尿苷100 mg）的药代动力学（PK）曲线下面积与静脉注射地西他滨相当。本项Ⅰ/Ⅱ期临床试验旨在评估口服DEC-C联合维奈克拉治疗年龄≥75岁或因合并症无法接受一线强化诱导化疗的AML患者（NCT04657081）。本文报告了该试验Ⅱ期部分的结果。方法：符合条件的患者在28天周期内接受口服DEC-C（1-5天）和维奈克拉400 mg/d治疗，第一周期维奈克拉剂量逐步增加（第1天100 mg，第2天200 g，第3天及之后400 g）。第一周期骨髓检查为可选，依据疗效和血细胞恢复情况调整维奈克拉和/或DEC-C的剂量。主要终点为完全缓解（CR）率，基于欧洲白血病网（ELN）2017年的疗效标准。结果：截至2024年9月30日，共有101名患者入组并完成了中位4个周期（范围：1-15周期）治疗。患者中位年龄为78岁。根据ELN 2017年分类，预后良好、中等和不良的患者分别占31.7%、33.7%和29.7%。中位随访时间为11.2个月。CR率和CR/CR伴不完全血液学恢复率分别为46.5%（95%CI：36.5%–56.7%）和63.4%（95%CI：53.2%–72.7%）。中位CR达成时间为2.4个月。中位CR持续时间未达到；在达到CR的患者中，80.0%在6个月时保持CR，75.3%在12个月时保持CR。中位总生存期为15.5个月（95% CI：7.6–无法估算）。98.0%的患者报告了≥3级的治疗相关不良事件，最常见的是发热性中性粒细胞减少症（49.5%）、贫血（38.6%）和中性粒细胞减少症（35.6%）。30天和60天死亡率分别为3.0%和9.9%。药代动力学数据显示口服DEC-C与维奈克拉之间不存在药物相互作用。结论：对于不适合接受强化诱导化疗的初诊AML患者，DEC-C联合VEN的全口服方案与静脉注射阿扎胞苷联合维奈克拉方案的安全性、缓解率和生存率相当。这些数据支持DEC-C联合维奈克拉可作为该类患者的治疗选择。专家解读姜尔烈教授：该方案是目前首个用于急性髓系白血病（AML）患者，特别是老年AML患者的全口服治疗方案。根据目前Ⅱ期研究结果，该方案的血液学缓解率接近50%，而整体缓解率则更高，接近70%。研究中入组的患者均为老年人，且中位年龄超过70岁。疗效方面，研究显示该方案能够实现显著的缓解，并且在生存期方面也表现出显著的临床获益，患者的中位总生存期达到15个月以上。在安全性方面，患者的主要不良反应为血液学毒性，三级及以上的血小板减少和中性粒细胞减少的发生率约为20%，这一数据表明，从安全性角度来看，该治疗方案具有较好的耐受性。重磅研究二Ziftomenib治疗复发/难治性（R/R）NPM1突变急性髓系白血病（AML）：来自关键性KOMET-001研究的Ⅰb/Ⅱ期临床活性与安全性结果（摘要号：6506）背景：NPM1突变（NPM1-m）约占急性髓系白血病（AML）患者的30%。尽管目前已有风险分层方法，但近一半的患者会在一年内发展为复发/难治性（R/R）疾病，且此时化疗后的完全缓解（CR）率不足10%。Ziftomenib是一种强效、高选择性、口服、在研的Menin抑制剂，在单药治疗和联合治疗中对成人R/R NPM1突变和KMT2A重排AML患者表现出临床活性，600 mg/d作为NPM1突变单药治疗的Ⅱ期推荐剂量。本文展示了在关键性KOMET-001研究中，接受Ziftomenib单药治疗的NPM1突变患者的初步分析结果。方法：KOMET-001（NCT04067336）是一项多中心、开放标签的Ⅰ期/Ⅱ期研究，评估Ziftomenib在成人R/R AML患者中的疗效。在Ⅱ期中，NPM1突变的R/R AML患者接受Ziftomenib 600 mg  每日一次治疗。Ⅱ期的主要终点为完全缓解伴完全/部分血液学恢复（CR/CRh）；关键次要终点为复合完全缓解（CRc）、CR/CRh和CRc的持续时间以及安全性。以下分析包括来自Ⅰb/Ⅱ期的NPM1突变患者数据。结果：Ⅱ期的主要终点已达成（P=0.0058）。截至2024年12月20日，Ⅰb/Ⅱ期研究共入组112名患者（51%来自美国/加拿大，49%来自欧洲/英国），并接受Ziftomenib 600 mg每日一次治疗，中位随访时间为4.2个月。患者中位年龄为69岁（范围：22–86岁），56%为女性，83%为ECOG表现状态评分0–1，既往治疗中位数为2次（范围：1–7），其中60%的患者既往接受过维奈克拉（VEN）治疗，23%的患者既往接受过移植治疗。在所有Ⅰb/Ⅱ期患者中，CR/CRh率为25%（28/112；95% CI：17-34），总缓解率为35%（39/112；95%CI：26-44）。在Ⅱ期研究中，23%（21/92；95% CI：15-33）患者达到了CR/CRh。在接受检测的CR/CRh应答患者中，67% (10/15) 的微小残留病 (MRD) 阴性。无论是否接受过VEN治疗，CR/CRh率均较为相似（VEN初治组21% vs. VEN暴露组24%）。Ziftomenib耐受性良好，3%（3/112）患者因治疗相关不良事件（TRAEs）中断治疗。40%（45/112）患者出现≥3级TRAEs，常见的不良事件包括13%的分化综合征（均为3级），贫血、发热性中性粒细胞减少症和血小板减少症各≤5%，以及2%的QTc延长（3级）。将呈现更新的临床活性和安全性数据。结论：在关键性KOMET-001研究中，Ⅱ期的主要终点已达成：Ziftomenib在R/R NPM1突变AML患者中取得了深度且持久的疗效，无论是否曾接受过VEN治疗。Ziftomenib耐受性良好，造血抑制有限，且仅有3%的患者因Ziftomenib相关不良事件中断治疗。综合这些数据，支持Ziftomenib单药治疗作为R/R NPM1突变AML患者的新治疗选择的潜力。专家解读姜尔烈教授：该研究讨论了Menin抑制剂的单药治疗，其CR率也表现出较好的效果，超过了20%，接近30%。目前，该药物正计划开展Ⅲ期临床研究，探索其与维奈克拉、阿扎胞苷的联合应用，或与经典的3+7方案联合使用。这项Ⅲ研究尤其是Menin抑制剂与维奈克拉或阿扎胞苷的联合应用有很大潜力。通过三药联合，预计可以进一步提高缓解率。今天的讨论主要集中在难治复发患者的治疗，但后续临床研究主要针对初治患者。预计在这一群体中，Menin抑制剂联合其他药物的治疗方案将取得更高的缓解率。目前其他分子靶向药物，如FLT3 抑制剂、IDH抑制剂、RAS抑制剂和Menin抑制剂等，联合低强度化疗在未来可能成为一种替代传统化疗的策略。这些药物的联合使用不仅可能提高一线治疗的缓解率，还能降低诱导治疗相关的死亡率，改善患者的安全性。因此，小分子靶向药物与非细胞毒药物的联合应用，已然成为当前研究的热点领域。未来，这类联合方案有望发展为可替代传统细胞毒治疗的安全有效方案，为AML的治疗带来新的变革。专家简介姜尔烈 教授中国医学科学院血液病医院（中国医学科学院血液学研究所）干细胞移植中心主任医学博士、主任医师、博士生（后）导师中国初级卫生保健基金会造血干细胞移植专委会主任委员CSCO白血病专委会主任委员中国血液病专科联盟白血病自体移植协作组组长中华医学会血液学分会造血干细胞应用学组副组长中国抗癌协会血液肿瘤专业委员会常务委员，造血干细胞移植与细胞治疗学组副组长CSCO自体造血干细胞移植工作组副组长天津市抗癌协会常务理事天津市血液与再生医学学会副理事长《中华血液学杂志》、《白血病·淋巴瘤》等杂志编委（来源：《肿瘤瞭望–血液时讯》编辑部）声 明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。