Randomised Phase II open-label window of opportunity trial AKTivate - Identifying target engagement and biomarkers of response, including an imaging biomarker, in participants receiving Capivasertib plus Exemestane and Capivasertib alone in post-menopausal participants with oestrogen receptor positive (ER+) early-stage breast cancer

开始日期2025-10-01

申办/合作机构

Cambridge University Hospitals NHS Foundation Trust

NCT06613516

/ Not yet recruiting临床2期IIT

CaptAin - Effect of Capivasertib on ctDNA in ER Positive Breast Cancer

There is growing evidence that cancer DNA (called circulating tumour DNA - ctDNA) in the blood is often an early sign that the cancer is likely to return. The aim of this study is to investigate whether treating women who have detectable ctDNA in their blood with a drug called Capivasertib can help control ctDNA levels and prevent developing metastatic or secondary breast cancer.
A recruitment of 20 women with oestrogen receptor (ER) positive breast cancer (who are already on standard of care hormone therapy who are being treated with curative intent) is aimed for; which means that the disease has not yet spread to distant parts of the body. Each subject will be dosed with 400mg of Capivasertib twice a day for a maximum period of two years.

开始日期2025-02-01

申办/合作机构

Imperial College London

[+3]

NCT06764186

/ Recruiting临床3期

A Phase IIIB Study to Evaluate the Use of Capivasertib in Combination With Fulvestrant in Patients With HR+ / HER2- Advanced Breast Cancer Who Have Relapsed/Progressed on ET and CDK4/6 Inhibitor Reflecting Real World Clinical Practice in Spain

The purpose of this study is to evaluate the effectiveness and safety of capivasertib + fulvestrant treatment administration in patients with locally advanced (inoperable) or metastatic HR+ / HER2- breast cancer with PIK3CA/AKT1/PTEN-altered following recurrence or progression on or after endocrine therapy and CDK4/6 inhibitor.

开始日期2025-01-07

申办/合作机构

AstraZeneca PLC

[+2]

100 项与卡帕塞替尼相关的临床结果

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100 项与卡帕塞替尼相关的转化医学

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100 项与卡帕塞替尼相关的专利（医药）

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405

项与卡帕塞替尼相关的文献（医药）

2025-04-01·MOLECULAR DIVERSITY

An in silico approach to identify novel and potential Akt1 (protein kinase B-alpha) inhibitors as anticancer drugs

Article

作者: Etikyala, Umadevi ; Manga, Vijjulatha ; Dalimba, Udayakumar ; Reddyrajula, Rajkumar ; Vani, T ; Kuchana, Vinutha

Akt1 (protein kinase B) has become a major focus of attention due to its significant functionality in a variety of cellular processes and the inhibition of Akt1 could lead to a decrease in tumour growth effectively in cancer cells. In the present work, we discovered a set of novel Akt1 inhibitors by using multiple computational techniques, i.e. pharmacophore-based virtual screening, molecular docking, binding free energy calculations, and ADME properties. A five-point pharmacophore hypothesis was implemented and validated with AADRR38. The obtained R² and Q² values are in the acceptable region with the values of 0.90 and 0.64, respectively. The generated pharmacophore model was employed for virtual screening to find out the potential Akt1 inhibitors. Further, the selected hits were subjected to molecular docking, binding free energy analysis, and refined using ADME properties. Also, we designed a series of 6-methoxybenzo[b]oxazole analogues by comprising the structural characteristics of the hits acquired from the database. Molecules D1-D10 were found to have strong binding interactions and higher binding free energy values. In addition, Molecular dynamic simulation was performed to understand the conformational changes of protein-ligand complex.

2025-03-01·PHARMACOECONOMICS

Cost-Effectiveness of Capivasertib as a Second-Line Therapy for Advanced Breast Cancer

Article

作者: Mital, Shweta ; Nguyen, Trang T H

BACKGROUND:

Capivasertib, a first-in-class AKT inhibitor, was recently approved as a second-line treatment for advanced breast cancer. However, capivasertib is expensive, raising questions over its economic value. This study provides the first evidence on the cost effectiveness of adding capivasertib to endocrine therapy (fulvestrant) for patients with PIK3CA/AKT1/PTEN-altered, hormone receptor-positive (HR⁺) human epidermal growth factor receptor 2-negative (HER2^-) advanced breast cancer.

METHODS:

A Markov model was built to compare the costs and effectiveness of three treatment strategies. The first strategy involved adding capivasertib to fulvestrant for all patients, while the second strategy involved adding it for only postmenopausal women. The third strategy involved treatment with fulvestrant alone. Analyses were conducted from a US payer perspective over a lifetime horizon. Costs were measured in 2023 US dollars, and effectiveness was measured in life years (LYs) and quality adjusted life years (QALYs), discounted at 3% per year. One-way sensitivity analyses, probabilistic sensitivity analyses, and scenario analyses were conducted to assess the robustness of results.

RESULTS:

The addition of capivasertib to fulvestrant for all patients was associated with $410,765 higher costs and 1.46 additional quality adjusted life years (QALYs) compared with fulvestrant alone, resulting in an incremental cost effectiveness ratio of $280,854/QALY. The strategy of adding capivasertib for only patients who are postmenopausal was extended dominated, i.e., yielded fewer QALYs at a higher cost per QALY than if capivasertib was added for all patients. These results were found to be robust in sensitivity and scenario analyses.

CONCLUSIONS:

At its current price, our analysis suggests that the addition of capivasertib to fulvestrant as a second line treatment is not cost effective versus fulvestrant alone at a willingness-to-pay threshold of $100,000/QALY. The price of capivasertib will need to be reduced by nearly 70% (to $7000 per cycle) for it to become cost effective.

2025-03-01·Molecular Therapy-Methods & Clinical Development

Capivasertib enhances chimeric antigen receptor T cell activity in preclinical models of B cell lymphoma

Article

作者: Kwak, Larry W ; Forman, Stephen J ; Hsieh, Hui-Ju ; Clark, Mary C ; Urak, Ryan ; Wang, Xiuli

Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling is involved in the growth of normal and cancer cells and is crucial for T cell activation. Previously, we have shown that AKT Inhibitor VIII, a selective AKT-1/2 inhibitor, during chimeric antigen receptor (CAR) T cell manufacturing, improves CAR T cell function in preclinical models. Although AKT Inhibitor VIII could enhance CAR T cell function, AKT Inhibitor VIII is not a clinical-grade compound. However, pan-AKT inhibitors have been applied against cancers with PIK3CA/AKT/PTEN alterations in clinical trials. We evaluated ex vivo and in vivo strategies of enhancing CAR T cell therapeutic effect using the pan-AKT inhibitor capivasertib. We found that ex vivo 0.25 μM capivasertib treatment during the period of T cell stimulation during manufacture enhanced the antitumor activity of CAR T cells in B cell lymphoma mouse models. Mechanistically, capivasertib changed gene and protein expression patterns related to the functions of memory and effector CAR T cells. Furthermore, in vivo combination therapy of capivasertib and CD19-specific CAR T cells led to improved early response to and persistence of functional CAR T cells in mice bearing PTEN-deficient lymphoma cells compared to CAR T cells alone. Capivasertib exerts a similar function to AKT Inhibitor VIII in modulating CAR T cells, and combining CAR T cell therapy with capivasertib both ex vivo and in vivo offers the potential to improve patient outcomes. Since PTEN deficiency is common in cancer and is the main mechanism for capivasertib function, combination therapy may provide an alternative solution for the challenges of CAR T cell therapy.

255

项与卡帕塞替尼相关的新闻（医药）

2025-03-22

·精准药物

【J. Med.Chem.】从弱到强：基于片段药物设计（FBBD）的40年突破之路

基于片段的药物设计（FBDD）已成为药物发现的重要策略，与传统高通量筛选（HTS）形成互补。历经近50年发展，推动多款药物成功上市。结构与计算工具的整合，显著提升FBDD效率，助力理性药物设计。随着药物靶点向“不可成药”领域及新治疗模式延伸，FBDD在靶向复杂生物分子中展现关键潜力。持续融合前沿计算与筛选技术（如虚拟筛选、机器学习），突破药物化学瓶颈，加速创新疗法开发。小片段撬动大突破自1981年提出以来，基于片段的药物设计（FBDD）已成为药物发现的核心策略之一。其核心逻辑是筛选低分子量化合物（约150–300 Da），这些片段虽与靶蛋白结合较弱，但通过化学修饰可优化为强效药物。1990年代，“核磁共振（SAR by NMR）”技术首次实现片段筛选，随后X射线晶体学、表面等离子体共振（SPR）等方法进一步推动技术普及，使FBDD融入主流药物研发流程。成果斐然：从“不可成药”到临床突破 FBDD已催生8款FDA批准药物及超50个临床候选化合物。首款成功案例是2011年获批的黑色素瘤药物Zelboraf，其研发仅用6年。随后，多款里程碑药物涌现： Pexidartinib（2015年）：一种CSF-1R抑制剂； Venetoclax（ABT-199，2016年）：一种Bcl-2抑制剂，能够破坏蛋白–蛋白相互作用； Erdafitinib（2019年）：一种用于治疗尿路上皮癌的FGFR抑制剂； Berotralstat（BCX7353，2020年）：一种用于治疗遗传性血管水肿的丝氨酸蛋白酶抑制剂； Sotorasib（AMG 510，2021年）：一种KRAS-G12C抑制剂，针对一个被认为难以治疗的“不可药化”蛋白； Asciminib（ABL001，2021年）：一种新型的BCR-ABL1别构抑制剂； Capivasertib（AZD5363，2023年）：一种AKT激酶抑制剂。超半数药物为激酶抑制剂，但Venetoclax和Sotorasib的成功证明FBDD在难治靶点中的潜力。此外，FBDD在苗头化合物优化、靶点可药性评估中展现高效性，甚至延伸至PROTAC等新兴疗法，成为药物创新的“多面手”。图1. 过去四十年基于片段的药物设计里程碑。3D分子结构由Schrödinger 2022.3（Maestro 13.3）中的LigPrep模块生成。图2. 从基于片段的药物设计（FBDD）衍生的FDA批准药物。展示了从FBDD衍生的FDA批准药物的化学结构。基于片段的药物设计（FBDD）：优势与挑战并存（1）优势： FBDD能筛选来自广泛化学空间的小分子片段，适用于各种靶点，包括蛋白质和RNA，具有较强的靶点适应性。片段库由低分子量化合物组成，通常遵循“三原则”，这使得它们在优化时具有更大潜力。 FBDD还可以通过敏感的筛选方法检测弱结合物，这些物质通常在高通量筛选中被忽略。片段筛选的时间较短，能够显著降低成本和时间。此外，FBDD能初步评估靶点的可药物性，帮助风险评估，无需参考化合物，易于实施。片段扩展有助于探索结构-活性关系（SAR），推动新型先导化合物开发。FBDD已应用于新型治疗模式，如PROTACs，利用片段连接原理，具有低分子量和弱结合亲和力，表明其在优化新药模式中的潜力。（2）挑战：片段库质量：需平衡多样性、合成可行性与理化性质，构建高质量库难度高；筛选灵敏度：弱结合检测依赖先进技术（如NMR、X射线），设备与经验门槛较高；苗头物选择：高命中率下需结合配体效率（LE）、结合模式分析（NMR/冷冻电镜）筛选优质片段；规模压力：百万级片段库涌现，传统实验筛选难以负荷，需虚拟筛选预筛以降低成本；人工优化局限：片段扩展依赖药物化学经验，面对海量数据与复杂相互作用，效率受限。表1. 片段筛选方法筛选方法样品要求灵敏度（亲和力）优势缺点配体观察NMR（STD-NMR, Water-LOGSY, CMPG, T1rho）低（<50 μM样品） mM–nM 不需要同位素标记。无法检测紧密结合物。对靶标大小没有限制。不适用于所有靶标。灵敏度高，能检测弱结合物。无法检测紧密结合物。可在筛选中使用片段混合物。 19F-NMR 低（<50 μM样品） mM–μM 灵敏的筛选方法。片段需要用氟标记。高通量筛选方法。只能检测弱结合物。适用于蛋白质和RNA靶标。不需要靶标标记，对靶标没有大小限制。蛋白质观察NMR（HSQC, 19F-NMR）高（>10 μM, 10–100 mg） mM–nM 可检测紧密结合物和弱结合物。需要标记蛋白质。提供结构信息。筛选时间较长。确定结合位点。 X射线晶体学高（10–50 mg） mM–nM 提供结构信息。无法检测结合亲和力和特异性。检测结合模式。需要高质量的晶体进行浸泡。表面等离子共振（SPR）低（<1 mg） μM–nM 高通量筛选方法。需要将靶标固定。提供筛选中的结合动力学数据。需要参考化合物设置实验。不适用于所有靶标。不适用于检测弱结合物。等温滴定量热法（ITC）高（>10 μM样品） μM–nM 提供结合曲线来测量结合亲和力。低通量实验。确定焓变或熵驱动的结合。需要较高浓度的样品。不适用于每个靶标。需要参考化合物设置实验。不适用于检测弱结合物。热变性实验（TSA）/差示扫描荧光法（DSF）低（∼μM–nM） μM–nM 高通量筛选实验假阳性率较高。不适用于每个靶标。需要参考化合物设置实验。本征质谱法低（nM, μg–1 mg） μM–nM 高通量筛选实验需要仔细优化实验条件。只需要微克级样品。不适用于弱结合物。微尺度热泳动法（MST）低（<μM） μM–nM 能测量结合亲和力。低通量筛选方法。不适用于弱结合物。生物层干涉法（BLI）低（∼μM） μM–nM 高通量方法不适用于弱结合物。适用于确认苗头化合物。荧光偏振法（FP）低（<μM） μM–nM 高通量筛选方法不适用于弱结合物。不适用于每个靶标。需要参考化合物设置实验。表型筛选无要求 μM–nM 筛选具有良好细胞渗透性的化合物。命中率低，需要确认靶标-苗头化合物的相互作用。适用于筛选共价片段仅适用于紧密结合物。不需要纯化靶标。需要确认靶标。生化实验低（<μM） μM–nM 高通量筛选实验靶标需要具有酶活性或已被充分表征。可以直接测量片段对靶标的影响。不适用于弱结合物，导致命中率低。筛选过程中需要较高浓度的片段。虚拟筛选无要求无要求高通量方法假阳性率高。筛选过程中不需要化合物和样品。需要通过实验筛选确认苗头化合物。适合筛选百万至十亿个化合物。能够考虑多个结合口袋。展望基于片段的药物设计（FBDD）有望成为药物发现的关键驱动力。随着分子生物学和生物信息学的进展，靶标空间已扩展到RNA及RNA结合蛋白（RBPs），为治疗提供了超越传统蛋白靶标的新机遇。例如，FDA批准的RNA剪接调节剂Risdiplam，通过调节SMN2前mRNA的剪接，成功治疗了相关疾病。然而，RNA及RBPs的极性和灵活性使得传统方法难以靶向，而FBDD凭借识别小分子和弱结合片段的优势，提供了有效的探索途径。高分辨率的冷冻电子显微镜（cryo-EM）揭示了复杂的蛋白质/RNA结构，帮助发现潜在的结合位点。同时，人工智能和分子建模技术加强了对RNA和蛋白质复合物的理解，提供了更精确的药物设计线索。多样化的片段库扩展了化学空间，结合实验和计算筛选提高了命中率和靶点识别能力。 FBDD与新兴计算技术的结合，使得药物设计更加强大和多功能。未来，FBDD有望攻克难以靶向的复杂靶标，如蛋白质-蛋白质相互作用和RNA靶点。将机器学习和人工智能整合到FBDD中，将加速药物发现过程，解决未满足的医学需求。参考文献： https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c00424

蛋白降解靶向嵌合体上市批准临床结果

2025-03-13

·PRNewswire

VERZENIO's Market Potential Soars as Demand for CDK4/6 Inhibitors Grows | DelveInsight

As VERZENIO gains traction in early-stage treatments and broadens its approved uses, its revenue is expected to keep growing. While the global CDK4/6 inhibitor market remains highly competitive, VERZENIO's distinct clinical advantages and ongoing studies could contribute to further market expansion. LAS VEGAS, March 13, 2025 /PRNewswire/ -- DelveInsight's " VERZENIO Market Size, Forecast, and Market Insight Report" highlights the details around VERZENIO, which is a targeted treatment known as a CDK4/6 inhibitor. The drug is a non-chemotherapy oral tablet. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of VERZENIO. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Eli Lilly and Company's VERZENIO (abemaciclib) Overview VERZENIO (abemaciclib) is a prescription medication used to treat adults with HR-positive, HER2-negative breast cancer that has metastasized (spread to other parts of the body). It is administered orally and is prescribed in combination with an aromatase inhibitor as an initial endocrine-based therapy. Additionally, the drug is being developed for the treatment of prostate cancer. VERZENIO is approved for the following indications: In combination with endocrine therapy for the adjuvant treatment of adults with HR+/HER2-, node-positive, early-stage breast cancer at high risk of recurrence. In combination with an aromatase inhibitor as the initial endocrine-based therapy for adults with HR+/HER2- advanced or metastatic breast cancer. In combination with fulvestrant for adults with HR+/HER2- advanced or metastatic breast cancer that has progressed after prior endocrine therapy. As monotherapy for adults with HR+/HER2- advanced or metastatic breast cancer that has progressed following endocrine therapy and prior chemotherapy in the metastatic setting. Learn more about VERZENIO projected market size for breast cancer @ VERZENIO Market Potential HR+/HER2- breast cancer is the most common subtype of breast cancer, defined by the presence of estrogen and progesterone hormone receptors but lacking HER2 overexpression. This form of breast cancer generally has a favorable prognosis and is primarily managed with hormone therapy to suppress hormone-driven tumor growth. According to DelveInsight's estimates, around 211,000 new cases of HR+/HER2− breast cancer were reported in the US in 2024. Over the past decade, endocrine therapy has remained the cornerstone of treatment, including for cases with visceral involvement. The current preferred approach involves combining endocrine therapy—using aromatase inhibitors or fulvestrant—with CDK4/6 inhibitors. The approval of CDK4/6 inhibitors has significantly transformed the treatment landscape for HR+/HER2− breast cancer. Currently, five selective CDK4/6 inhibitors— ENHERTU, DATROWAY, IBRANCE, KISQALI, and VERZENIO—are used in combination with endocrine therapy. In November 2023, the FDA approved TRUQAP (capivasertib) in combination with FASLODEX for patients with advanced HR+/HER2− breast cancer harboring specific biomarker alterations (PIK3CA, AKT1, or PTEN). The NCCN Guidelines have designated KISQALI as the only Category 1 Preferred CDK4/6 inhibitor for first-line treatment in combination with an aromatase inhibitor, strengthening its position in the U.S. market. This led to KISQALI recovering its lost market share, with its U.S. revenue contribution rebounding to 50%, following declines to 46% in 2020, 36% in 2021, and 38% in 2022. In January 2025, the FDA approved DATROWAY for patients with unresectable or metastatic HR+/HER2- breast cancer (IHC 0, IHC 1+, or IHC 2+/ISH-) who had previously received endocrine-based therapy and chemotherapy. Additionally, ENHERTU was approved for patients with unresectable or metastatic HR+, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer that had progressed after at least one prior endocrine therapy in the metastatic setting. Also, in January 2025, Roche reported positive topline results from its Phase III INAVO120 trial, assessing ITOVEBI in combination with IBRANCE and fulvestrant for patients with PIK3CA-mutated HR+/HER2−, endocrine-resistant, locally advanced, or metastatic breast cancer. Among the seven major markets, the US accounted for the largest market share in HR+/HER2− breast cancer, generating USD 7.5 billion in revenue in 2023. The market is expected to experience substantial growth from 2025 to 2034, driven by the introduction of novel therapeutic options. Discover more about the breast cancer market in detail @ Metastatic HR+/HER2- Breast Cancer Market Report Emerging Competitors of VERZENIO Some of the competing emerging key players in HR+/HER2- breast cancer market are, Merck (KEYTRUDA), Arvinas (ARV-471 (vepdegestrant)), Olema Pharmaceuticals (OP1250 (palazestrant)), Celcuity (Gedatolisib), Roche (Giredestrant (RG6171, GDC-9545); Inavolisib), AstraZeneca and Daiichi Sankyo (Datopotamab Deruxtecan (Dato-DXd)), AstraZeneca (Camizestrant (AZD9833); Capivasertib), Eli Lilly (LY3484356/Imlunestrant), Sermonix Pharmaceuticals (Lasofoxifene), Veru Pharma (Enobosarm), DualityBio/BioNtech (DB-1303), Evgen Pharma (SFX-01), Carrick Therapeutics (Samuraciclib (CT-7001)), EQRx/G1 Therapeutics (Lerociclib), Immutep (Eftilagimod Alpha (LAG-3lg/IMP321)), and others. To know more about the number of competing drugs in development, visit @ VERZENIO Market Positioning Compared to Other Drugs Key Milestones of VERZENIO In 2024, Phase III trials did not meet primary endpoints or were terminated for futility. Negative Phase III CYCLONE-2 results, in which VERZENIO added to abiraterone did not meet the primary endpoint of improved radiographic progression-free survival (rPFS) in men with metastatic castration-resistant prostate cancer (mCRPC). In December 2023, Eli Lilly and Company presented results from the MONARCH 3 clinical trial at the 2023 San Antonio Breast Cancer Symposium (SABCS). Results from MONARCH 3 show a numerical improvement in overall survival (OS) of 13.1 months for women with HR+, HER2- metastatic breast cancer treated with VERZENIO plus an aromatase inhibitor in the intent-to-treat population and 14.9 months for women with visceral disease. In March 2023, the US FDA approved an expanded indication for VERZENIO in combination with endocrine therapy for the adjuvant treatment of adult patients with HR+/HER2−, node-positive, early breast cancer (EBC) at a high risk of recurrence. This expanded adjuvant indication removes the Ki-67 score requirement for patient selection. In February 2022, the CHMP adopted a positive opinion recommending a change to the terms of the marketing authorization for the medicinal product VERZENIO. VERZENIO, in combination with endocrine therapy, is indicated for the adjuvant treatment of adult patients with HR+/HER2− negative, node-positive early breast cancer at high risk of recurrence. In October 2021, the US FDA approved VERZENIO, in combination with endocrine therapy (tamoxifen or an aromatase inhibitor), for the adjuvant treatment of adult patients with HR+/HER2−, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of ≥20% as determined by an FDA-approved test. Ki-67 is a marker of cellular proliferation. In September 2018, VERZENIO was approved in Europe for treating advanced HR+ breast cancer in women if the cancer has already spread to other parts of the body or is locally advanced. In September 2018, VERZENIO was approved for the treatment of patients with HR+/HER2− unresectable or recurrent breast cancer in combination with fulvestrant or an aromatase inhibitor (AI) in Japan. In February 2018, the US FDA approved VERZENIO in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy for the treatment of postmenopausal women with HR+/HER2− advanced or metastatic breast cancer In September 2017, the US FDA approved VERZENIO in combination with an endocrine therapy to treat adult patients who have HR+/HER2− advanced or metastatic breast cancer that has progressed after taking therapy that alters a patient's hormones (endocrine therapy). In October 2015, the US FDA granted Breakthrough Therapy Designation to abemaciclib for patients with refractory hormone-receptor-positive (HR+) advanced or metastatic breast cancer Discover how VERZENIO is shaping the breast cancer treatment landscape @ VERZENIO Breast Cancer VERZENIO Market Dynamics The oral administration of VERZENIO enhances patient convenience, while its expanded approval for the adjuvant treatment of adult patients with HR+/HER2- early breast cancer highlights its role as a differentiated CDK4/6 inhibitor in reducing the risk of recurrence. The rising prevalence of HR+/HER2- breast cancer is driving market demand for effective treatments like VERZENIO. Additionally, its demonstrated efficacy in combination with endocrine therapy and its ability to penetrate the central nervous system further strengthen its market position. Favorable reimbursement policies and increasing awareness among healthcare providers also contribute to its adoption. However, its adoption may be hindered by regulatory hurdles and potential side effects, including severe or life-threatening lung inflammation and serious liver problems. High treatment costs and access disparities in certain regions could also limit market penetration. Competition from other CDK4/6 inhibitors such as IBRANCE and KISQALI poses a challenge, along with concerns over long-term safety data. Additionally, the Phase III CYCLONE-2 trial failed to meet primary endpoints in mCRPC, which may impact its broader clinical prospects and investor confidence. Dive deeper to get more insight into VERZENIO's strengths & weaknesses relative to competitors @ VERZENIO Market Drug Report Table of Contents Related Reports CDK4/6 Inhibitor Market CDK4/6 Inhibitor Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key CDK4/6 inhibitor companies including Pfizer, Prelude Therapeutics, G1 Therapeutics, Pepper Bio, among others. Metastatic HR+/HER2− Breast Cancer Market Metastatic HR+/HER2− Breast Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key metastatic HR+/HER2− breast cancer companies including Pfizer, Novartis, Stemline Therapeutics, Olema Pharmaceuticals, Arvinas, Immutep, AstraZeneca, Roche, Genentech, Evexta Bio, EQRx, Sermonix Pharmaceuticals, Celcuity, Veru Pharma, Evgen Pharma, Eli Lilly, Biotheryx, among others. HR+/HER2− Breast Cancer Pipeline HR+/HER2− Breast Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key HR+/HER2− breast cancer companies, including Regor Therapeuics, Seagen Inc., CytomX Therapeutics, Taizhou EOC Pharma, Chia Tai Tianqing Pharmaceutical Group, AstraZeneca, Daiichi Sankyo, Inc., Tyme, Inc., Seagen Inc., Context Therapeutics, Eisai Inc., Shanghai Hengrui Pharmaceutical Co., Ltd., Jiangsu Simcere Pharmaceutical Co., Kind Pharmaceuticals, Merus N.V., Atossa Therapeutics, Roche, among others. Breast Cancer Market Breast Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key breast cancer companies, including Veru, Sanofi, Roche, AstraZeneca, Eli Lilly, EQRx, Gilead, Sermonix Pharmaceuticals, Evgen Pharma, Tyme, Genentech, Daiichi Sankyo, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期上市批准临床结果突破性疗法ASCO会议

2025-03-07

·九洲药业

【速递】关爱女性健康，盘点近期FDA获批新药

在第115个国际劳动妇女节到来之际，女性健康问题再次聚焦了大家的目光，下面盘点一下近两年美国FDA获批用于治疗女性疾病的新药。 Elacestrant 2023年1月27日，FDA批准了elacestrant用于治疗至少接受一线内分泌治疗后疾病出现进展的ER阳性、HER2阴性、ESR1突变的晚期或转移性乳腺癌。 Elacestrant是一款口服SERD（选择性ER受体降解剂）。该适应症的批准基于EMERALD试验，主要疗效结果指标是无进展生存期（PFS），由盲法影响审查委员会评估。在意向治疗（ITT）人群和ESR1突变患者亚组中观察到PFS具有统计学显著差异。在228名（48%）患有ESR1突变的患者汇总，elacestrant组的中位PFS为3.8个月（95%CI:2.2,7.3），氟维司群或芳香化酶抑制剂组的中位PFS为1.9个月（95%CI:1.9,2.1）(风险比[HR]为0.55[95%CI:0.39,0.77]，双侧p值=0.0005)。对250名（52%）没有ESR1突变的患者的PFS进行探索性分析显示HR为0.86（95%CI:0.63,1.19），表明ITT人群的改善主要归因于ESR1突变人群中看到的结果。下图A和C为所有人群，B和D为ESR1突变人群。最常见的不良事件（≥10%）包括肌肉骨骼疼痛、恶心、胆固醇升高、AST升高、甘油三酯升高、疲劳、血红蛋白降低、呕吐、ALT升高、钠降低、肌酐升高、食欲下降、腹泻、头痛、便秘、腹痛、潮热和消化不良。 Fezolinetant 2023年5月12日，美国FDA批准了神经激肽3（NK3）受体拮抗剂fezolinetant用于治疗更年期引起的中度至重度血管舒缩症状或潮热。 FDA药品评估与研究中心罕见病、儿科、泌尿和生殖医学办公室主任、医学博士Janet Maynard表示：“更年期潮热会给女性带来严重的身体负担，影响她们的生活质量。引入一种治疗中度至重度更年期潮热的新分子将为女性提供另一种安全有效的治疗选择。” 更年期是女性生命中正常的自然变化，通常发生在45至55岁之间，此时女性的月经停止。更年期通常被称为“生命的改变”。在更年期期间，女性体内产生的雌激素和孕激素会逐渐减少。如果女性连续12个月没有月经，则表明她已进入更年期。大约 80% 的更年期女性会出现潮热，包括出汗、潮红和持续几分钟的寒冷。有些女性患有潮热，并且有阴道出血、中风、心脏病发作、血栓或肝病史，因此不能接受激素疗法。fezolinetant不是一种激素。它针对的是导致更年期潮热的神经活动。 Capivasertib 2023年11月16日，美国FDA批准AKT抑制剂capivasertib联合氟维司群用于治疗HR阳性、HER2阴性局部晚期或转移性乳腺癌成年患者，这些患者经FDA批准的检测检测出一种或多种PIK3CA/AKT1/PTEN改变，并且在转移性环境中接受至少一种内分泌方案治疗后出现进展，或在完成辅助治疗时或完成辅助治疗后12个月内出现复发。该适应症批准基于CAPltello-291试验，主要疗效结果指标是研究者评估的总体人群和肿瘤有PIK3CA/AKT1/PTEN变异的患者人群的PFS，根据RECIST 1.1版进行评估。总体人群和肿瘤有PIK3CA/AKT1/PTEN变异的患者人群的PFS 具有统计学显著差异。在289名PIK3CA/AKT1/PTEN变异肿瘤患者中，capivasertib-氟维司群组的中位PFS为7.3个月（95%CI：5.5, 9.0），安慰剂-氟维司群组的中位PFS为3.1个月（95%CI：2.0, 3.7）（风险比 [HR] 0.50 [95%CI：0.38, 0.65] p值< 0.0001）。对313名(44%)肿瘤未发生PIK3CA/AKT1/PTEN变异的患者的PFS进行探索性分析，结果显示HR为0.79（95%CI：0.61, 1.02），这表明总体人群的差异主要归因于肿瘤发生PIK3CA/AKT1/PTEN变异的患者人群的结果。最常见的不良反应（≥20％的患者报告），包括腹泻、皮肤不良反应、随机血糖升高、淋巴细胞减少、血红蛋白减少、空腹血糖升高、恶心、疲劳、白细胞减少、甘油三酯升高、中性粒细胞减少、肌酐升高、呕吐和口腔炎。 Ribociclib 2024年9月17日，美国FDA新增了CDK4/6抑制剂ribociclib一项适应症，联合芳香化酶抑制剂用于辅助治疗HR阳性、HER2阴性且复发风险较高的II期和III期早期乳腺癌成人患者。该适应症的批准基于NATALEE试验，主要疗效结果指标是无浸润性疾病生存期(iDFS)。iDFS定义为随机分配至以下情况的首次发生：局部或区域浸润性乳腺复发、远处复发、任何原因导致的死亡、对侧浸润性乳腺癌或继发性原发性非乳腺浸润性癌症（不包括皮肤基底细胞癌和鳞状细胞癌）。中期分析显示，意向治疗患者群体的iDFS显著改善。iDFS分析的疗效结果显示，ribociclib+芳香化酶抑制剂组36个月时的iDFS为90.7%（95%CI：89.3，91.8），芳香化酶抑制剂组为87.6%（95%CI：86.1，88.9），HR为0.749（95%CI：0.628，0.892）。在iDFS最终分析时，OS尚未成熟。 Inavolisib 2024年10月10日，美国FDA批准PI3Kα抑制剂inavolisib与palbociclib和氟维司群联合用于治疗经FDA批准的检测检测出内分泌耐药、PIK3CA突变、HR阳性、HER2阴性、局部晚期或转移性乳腺癌的成人患者，这些患者在完成辅助内分泌治疗期间或之后出现复发。该适应症的批准基于INAVO120试验，主要疗效结果指标是研究者评估的PFS（根据RECIST 1.1版）。 inavolisib+palbociclib+氟维司群组的中位PFS为15.0个月（95%CI：11.3, 20.5），安慰剂+palbociclib+氟维司群组的中位PFS为7.3个月（95%CI：5.6, 9.3）（HR 0.43 [95%CI：0.32, 0.59] p值<0.0001）。inavolisib+palbociclib+氟维司群组的ORR为58% (95%CI: 50, 66)，安慰剂+palbociclib+氟维司群组的ORR为25% (95%CI: 19, 32)。中位DOR分别为18.4个月 (95%CI: 10.4, 22.2) 和9.6个月 (95%CI: 7.4, 16.6)。基于63%信息分数的总生存期中期分析未达到统计学意义，但支持总体获益风险评估，HR为0.64 (95%CI: 0.43, 0.97)。最常见的不良反应（≥20%）包括中性粒细胞减少、血红蛋白减少、空腹血糖升高、血小板减少、淋巴细胞减少、口腔炎、腹泻、钙减少、疲劳、钾减少、肌酐升高、ALT升高、恶心、钠减少、镁减少、皮疹、食欲下降、COVID-19感染和头痛。临床在研AKT抑制剂结构图临床在研PI3Kα抑制剂结构图参考资料： 1.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-elacestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast-cancer 2.https://ascopubs.org/doi/10.1200/JCO.22.00338?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 3.https://www.fda.gov/news-events/press-announcements/fda-approves-novel-drug-treat-moderate-severe-hot-flashes-caused-menopause 4.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-fulvestrant-breast-cancer 5.https://www.nejm.org/doi/full/10.1056/NEJMoa2214131 6.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-kisqali-aromatase-inhibitor-and-kisqali-femara-co-pack-early-high-risk-breast-cancer 7.https://www.nejm.org/doi/full/10.1056/NEJMoa2305488 8.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-inavolisib-palbociclib-and-fulvestrant-endocrine-resistant-pik3ca-mutated-hr-positive 9.https://www.nejm.org/doi/full/10.1056/NEJMoa2404625 免责申明本公众号注明原创的内容权利均属九洲药业所有，未经授权，不得擅自使用或许可他人使用。如需获得授权，请和九洲药业提前联系。已获得授权的，应在授权范围内使用，并注明来源且不得再全部或部分转授权他人。本公众号对转载、分享的内容、陈述、观点判断保持中立，不对所包含内容的合法性、准确性、可靠性或完善性提供任何明示或暗示的保证，该等内容版权归原作者所有，仅供学习参考之用，若对转载、分享的内容有任何权利疑问，烦请联系九洲药业。

临床结果

100 项与卡帕塞替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11371	-	-	DB12218

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
ER阳性/HER2阴性乳腺癌	欧盟	AstraZeneca AB	2024-06-17
ER阳性/HER2阴性乳腺癌	冰岛	AstraZeneca AB	2024-06-17
ER阳性/HER2阴性乳腺癌	列支敦士登	AstraZeneca AB	2024-06-17
ER阳性/HER2阴性乳腺癌	挪威	AstraZeneca AB	2024-06-17
乳腺癌	加拿大	AstraZeneca Canada, Inc.	2024-01-26
HR阳性/HER2阴性乳腺癌	美国	AstraZeneca Pharmaceuticals LP	2023-11-16

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
局部晚期乳腺癌	临床3期	西班牙	AstraZeneca PLC	2025-01-07
晚期乳腺癌	临床3期	中国	AstraZeneca AB	2024-09-26
转移性去势抵抗性前列腺癌	临床3期	美国	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	中国	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	日本	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	澳大利亚	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	比利时	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	巴西	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	加拿大	AstraZeneca PLC	2022-03-25
转移性去势抵抗性前列腺癌	临床3期	智利	AstraZeneca PLC	2022-03-25

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临床结果

适应症

分期

评价

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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


NCT04305496 (CAPItello-291, Pubmed \| J Clin Oncol)	临床3期	PIK3CA突变/HR阳性/HER2阴性乳腺癌 PIK3CA \| AKT1 \| PTEN	708	Capivasertib 400 mg twice daily with fulvestrant	範窪壓鑰構餘積鹽淵築(製簾願鏇簾膚構築夢選): HR = 0.6 (95% CI, 0.51 ~ 0.71) 更多	积极	2024-12-01
				Placebo with fulvestrant
NCT04556773 (DESTINY-Breast08, SABCS2024) 人工标引	临床1期	HER2低表达乳腺癌 HER2-low	60	Trastuzumab deruxtecan (T-DXd) + Capecitabine (CAPE)	衊艱鏇繭壓衊壓憲鏇壓(鹹壓選艱襯糧齋憲衊製) = 範鑰網鹽糧構顧糧夢齋壓鏇壓繭範鑰衊範製觸 (鏇糧鏇廠簾獵遞願鏇繭 ) 更多	积极	2024-11-26
				Trastuzumab deruxtecan (T-DXd) + Capivasertib (CAPI)	衊艱鏇繭壓衊壓憲鏇壓(鹹壓選艱襯糧齋憲衊製) = 衊餘窪壓糧製夢築鏇齋壓鏇壓繭範鑰衊範製觸 (鏇糧鏇廠簾獵遞願鏇繭 ) 更多
NCT04493853 (CAPItello-281, Company_Website) 人工标引	临床3期	激素依赖性前列腺癌 PTEN Deficient Expression	-	capivasertib + abiraterone + androgen deprivation therapy	繭構鏇遞獵憲顧廠鹽遞(壓壓襯鹽艱夢積膚獵廠) = statistically significant and clinically meaningful improvement 鬱製醖夢顧願襯膚窪餘 (壓蓋鑰網餘窪願壓遞鏇 ) 更多	积极	2024-11-25
				placebo + abiraterone + androgen deprivation therapy
NCT04305496 (CAPItello-291, Pubmed \| Future Oncol)	临床3期	HR阳性乳腺癌 PIK3CA \| AKT1 \| PTEN	-	Capivasertib plus Fulvestrant	顧蓋壓廠夢襯醖鹹繭餘(廠鹹襯選繭糧選觸築鹹) = The most common side effects experienced by participants included diarrhea 糧艱醖積遞網餘醖鏇襯 (蓋繭憲壓繭製襯鏇齋餘 ) 更多	积极	2024-11-25
				Placebo plus Fulvestrant
NCT04305496 (CAPItello-291, Pubmed) 人工标引	临床3期	HR阳性/HER2阴性乳腺癌 HER2 Negative \| Hormone Receptor Positive	901	capivasertib + fulvestrant	鬱獵構選衊獵觸餘醖選(鑰膚繭襯鏇積遞艱鹹繭) = 遞淵鏇築齋壓淵襯選顧壓選夢選膚顧蓋餘構鹽 (鹽蓋蓋壓鏇壓積蓋顧繭, 9.1 ~ 16.7) 更多	积极	2024-09-01
				placebo + fulvestrant	鬱獵構選衊獵觸餘醖選(鑰膚繭襯鏇積遞艱鹹繭) = 鏇窪壓獵壓憲鬱獵襯製壓選夢選膚顧蓋餘構鹽 (鹽蓋蓋壓鏇壓積蓋顧繭, 2.0 ~ 16.4) 更多
NCT03997123 (CAPItello-290, Company_Website) 人工标引	临床3期	晚期三阴性乳腺癌 PIK3CA \| AKT1 \| PTEN	923	Truqap (capivasertib) in combination with paclitaxel	鹹願獵衊顧鏇範餘簾壓(壓鬱壓鏇餘鹹夢壓衊獵) = did not meet the dual primary endpoints of improvement in overall survival (OS) 齋糧積壓獵願鹹獵鑰積 (鏇鹹鹹夢壓構夢衊憲鹽 ) 未达到更多	不佳	2024-06-18
				paclitaxel in combination with placebo
NCT04305496 (CAPItello-291, ESMO_BC2024) 人工标引	临床3期	HR阳性/HER2阴性乳腺癌 HER2 Negative \| Hormone Receptor Positive	708	Capivasertib + Fulvestrant (Overall population)	範廠膚築製壓願窪窪壓(繭衊願鏇構艱壓築鏇鬱) = 製鏇鹹鹽獵窪衊廠繭餘憲繭糧醖鬱襯淵衊齋壓 (壓獵鑰築選鏇願糧淵鏇 ) 更多	积极	2024-05-16
				Placebo + Fulvestrant (Overall population)	範廠膚築製壓願窪窪壓(繭衊願鏇構艱壓築鏇鬱) = 蓋衊構製鬱衊壓獵製憲憲繭糧醖鬱襯淵衊齋壓 (壓獵鑰築選鏇願糧淵鏇 ) 更多
NCT04305496 (CAPItello-291, SABCS2023)	临床3期	HR阳性/HER2阴性乳腺癌	-	Capivasertib + Fulvestrant	窪鹽憲製鹹選構簾醖鹹(夢顧範窪鹽糧築遞夢構) = Diarrhea (mostly grade 1) was the most frequent adverse event 網製鹹鹹醖齋築範鹽蓋 (膚蓋構鑰製製遞構蓋網 ) 更多	-	2023-12-05
				Placebo + Fulvestrant
NCT04305496 (CAPItello-291, ESMO_ASIA2023)	临床3期	HR阳性/HER2阴性乳腺癌 PIK3CA \| AKT1 \| PTEN	134	Capivasertib + fulvestrant	襯窪製鹽齋鏇齋壓衊願(選膚遞衊壓鹹鏇選餘鏇) = 窪遞鬱鹽蓋壓窪獵觸鹹齋醖遞鑰鑰願鹽選繭鬱 (壓淵鹽壓夢獵憲鏇憲鏇 )	积极	2023-12-02
				Placebo + fulvestrant	襯窪製鹽齋鏇齋壓衊願(選膚遞衊壓鹹鏇選餘鏇) = 獵構鏇餘淵鏇鏇願蓋壓齋醖遞鑰鑰願鹽選繭鬱 (壓淵鹽壓夢獵憲鏇憲鏇 )
NCT04305496 (CAPItello-291, FDA) 人工标引	临床3期	HR阳性/HER2阴性乳腺癌 Hormone Receptor Positive \| HER2 Negative	708	TRUQAP+fulvestrant (PIK3CA/AKT1/PTEN-Altered Tumors)	範壓範遞糧鬱築獵鹹餘(製廠艱鹹醖願獵繭淵窪) = 網艱範夢繭壓繭廠蓋襯蓋觸襯繭獵糧齋繭簾築 (積鏇鏇醖齋網夢簾網鑰 ) 更多	积极	2023-11-16
				placebo+fulvestrant (PIK3CA/AKT1/PTEN-Altered Tumors)	範壓範遞糧鬱築獵鹹餘(製廠艱鹹醖願獵繭淵窪) = 範選構襯願壓壓構艱淵蓋觸襯繭獵糧齋繭簾築 (積鏇鏇醖齋網夢簾網鑰 ) 更多