This multicenter, prospective phase II clinical trial evaluates the efficacy and safety of sequential SHR-A1811 followed by dalpiciclib plus endocrine therapy (fulvestrant or aromatase inhibitors) in 45 patients with HR+/HER2-low/ultra-low advanced breast cancer. Enrolled patients will receive SHR-A1811 monotherapy for 6-8 cycles until clinical benefit, then transition to dalpiciclib with endocrine therapy until disease progression or unacceptable toxicity. The primary endpoint is progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), overall survival (OS), and treatment-related adverse events (TRAEs). The study will be conducted at Sun Yat-sen Memorial Hospital and collaborating centers.

开始日期2025-06-20

申办/合作机构

中山大学孙逸仙纪念医院

NCT06810492

/ Not yet recruitingN/AIIT

A Single-arm Exploratory Study of the Efficacy and Safety of CDK4/6 Inhibitors in Combination with Endocrine Therapy in the Neoadjuvant Treatment of HR+/HER2- Early Breast Cancer

To explore the efficacy and safety of CDK4/6 inhibitors combined with endocrine neoadjuvant therapy for stage II-III HR-positive/HER2-negative breast cancer.
This study adopts a single-arm, open-label design, and plans to include 40 patients with stage II-III HR+/HER2- breast cancer.

开始日期2025-04-01

申办/合作机构

湖北省肿瘤医院（湖北省肿瘤研究所）

NCT06711094

/ Not yet recruitingN/AIIT

Single-arm,Exploratory Clinical Study of Albumin-bound Paclitaxel Combination With Dalpiciclib and AI in the Treatment of ER-Low (1%-10%), HER2-negative Advanced Breast Cancer

This is a prospective, single-arm, single-center, open, exploratory clinical study.. Screening for histopathologically confirmed recurrent or metastatic ER-Low positive (1%-10%) and HER2-negative breast cancer patients who meet the inclusion criteria and have not previously received any systemic anticancer therapy for advanced disease, He was treated with albumin-bound paclitaxel in combination with Dalpiciclib and AI.

开始日期2025-01-01

申办/合作机构

福建医科大学

100 项与羟乙磺酸达尔西利相关的临床结果

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100 项与羟乙磺酸达尔西利相关的转化医学

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100 项与羟乙磺酸达尔西利相关的专利（医药）

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项与羟乙磺酸达尔西利相关的文献（医药）

2025-04-01·Cancer Communications

A prospective, phase II, neoadjuvant study based on chemotherapy sensitivity in HR+/HER2‐ breast cancer‐FINEST study

Article

作者: Liu, Guang‐Yu ; Li, Jun‐Jie ; Wu, Wen‐Ya ; Liang, Fei ; Wu, Jiong ; Chen, Li ; Yu, Ke‐Da ; Wang, Zhong‐Hua ; Di, Gen‐Hong ; Shao, Zhi‐Ming ; Fan, Lei

Abstract:

Background:

Hormone receptor‐positive (HR+)/humaal growth factor receptor 2‐negative (HER2‐) breast cancer, the most common breast cancer type, has variable prognosis and high recurrence risk. Neoadjuvant therapy is recommended for median‐high risk HR+/HER2‐ patients. This phase II, single‐arm, prospective study aimed to explore appropriate neoadjuvant treatment strategies for HR+/HER2‐ breast cancer patients.

Methods:

Eligible female patients with newly diagnosed, untreated HR+/HER2‐ breast cancer received 2 cycles of nab‐paclitaxel and carboplatin (nabPCb). Magnetic resonance imaging (MRI) was performed to assess tumor responses, and 40% regression of the maximal tumor diameter was deemed chemo‐sensitive. Chemo‐sensitive patients continued nabPCb for 4 more cycles (group A). Chemo‐insensitive patients were randomized to groups B, C, and D at a ratio of 1:3:1 to receive a new chemotherapy for 4 cycles or endocrine‐immune‐based therapy (dalpiciclib, letrozole and adebrelimab, with goserelin if patients were premenopausal) for 4 cycles or to undergo surgery. Peripheral blood and core‐needle biopsy (CNB) samples were collected before treatment, followed by a next‐generation sequencing (NGS) panel detection and similarity network fusion (SNF) typing through digital pathology data. The primary endpoint was the pathological complete response (pCR) rate, and the secondary endpoint was the clinical objective response rate (ORR).

Results:

A total of 121 patients were enrolled (67.8% with stage III disease), with 76, 9, 27, and 9 patients in groups A, B, C and D, respectively. The total pCR rate was 4.1%, and all patients who received pCR were in group A. Group C had a better ORR than Group B (81.5% vs. 66.7%). Exploratory analysis revealed that patients with the SNF4 subtype were the most sensitive to nabPCb (pCR rate of 21.1% vs. 1.8% in group A), whereas patients in group C with the SNF2 subtype were more sensitive to endocrine‐immune‐based therapy (Miller‐Payne grade 4‐5, 45.5% vs. 6.3%).

Conclusions:

Converting to endocrine‐immune‐based therapy improved the ORR, but not the pCR rate in chemo‐insensitive patients. Neoadjuvant chemotherapy and endocrine therapy are not mutually exclusive. The SNF4 subtype of HR+/HER2‐ breast cancer was more chemo‐sensitive, whereas the SNF2 subtype might be more sensitive to immunotherapy.

2025-02-01·BREAST

Influence of ethnicity on cyclin-dependent kinase inhibitor efficacy and toxicity: A systematic review and meta-analysis

Review

作者: De Santis, Pierluigi ; Pagliuca, Martina ; Arpino, Grazia ; De Laurentiis, Michelino ; Giuliano, Mario ; De Angelis, Carmine ; Pavone, Giuliana ; Longobardi, Alessandra ; Caputo, Roberta ; Caltavituro, Aldo ; Del Mastro, Lucia ; Puglisi, Fabio ; Tafuro, Margherita ; Buonaiuto, Roberto

BACKGROUND:

The combination of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard of care for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (aBC). While the efficacy and safety profiles of CDK4/6i and ET have been extensively evaluated in phase II and III trials worldwide, it remains unclear whether the response to CDK4/6i and toxicity profile vary among Asian and non-Asian patients. Therefore, we aimed to assess the treatment efficacy of ET with and without CDK4/6i by comparing outcomes in Asian and non-Asian subgroups included in these clinical trials. In addition, we evaluated the toxicity profiles of the treatments by estimating the risk of treatment-related adverse events (AEs).

METHODS:

We conducted a meta-analysis including the most recent randomized trial data systematically searched from PubMed, Embase, Web of Science, Cochrane CENTRAL (from inception to May 31st, 2024) or presented in abstracts or oral presentations at the ESMO, ASCO, and SABCS international congresses. We included studies comparing CDK4/6i (palbociclib, ribociclib, abemaciclib, dalpiciclib) + ET versus placebo + ET. Progression-free survival (PFS) and overall survival (OS), hazard ratios (HR), and 95 % confidence intervals (CI) were extracted for the two subgroups of interest. To evaluate the treatment-related toxicity profiles, we extracted the number of side effects to estimate the risk of treatment-emergent AEs.

RESULTS:

Eleven studies (n = 5129) were included in this meta-analysis. The addition of CDK4/6i to ET consistently improved PFS in both Asian (HR = 0.52, 95 % CI 0.47-0.60; p < 0.001) and non-Asian (HR = 0.58, 95 % CI 0.52-0.64; p < 0.001) groups. Similarly, the combination of CDK4/6i + ET led to an OS improvement in both Asian (HR = 0.75, 95 % CI 0.62-0.91; p = 0.003) and non-Asian (HR = 0.81, 95 % CI 0.73-0.89; p < 0.001) patients. The risk of treatment related toxicity was higher in the CDK4/6i + ET arm in both Asian and non-Asian groups. Interestingly, a numerically higher rate of treatment-related hematological toxicity was observed in Asian patients, although no significant interethnic difference was found in the relative risk of these events.

CONCLUSIONS:

The combination of CDK4/6i and ET significantly improves PFS and OS compared to ET alone in both Asian and non-Asian patients with HR+/HER2-aBC. Although the magnitude of benefit appears to be independent of ethnicity, future clinical trials should devise a standardized method for stratifying patients by ethnicity to more effectively assess potential differences in treatment benefits.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO registration number: CRD42024543217.

2025-01-23·JOURNAL OF MEDICINAL CHEMISTRY

Elucidating Binding Selectivity in Cyclin-Dependent Kinases 4, 6, and 9: Development of Highly Potent and Selective CDK4/9 Inhibitors

Article

作者: Xing, Yajie ; Cao, Qixiong ; Chen, Jiean ; Wang, Rui ; Yang, Qianqian ; Pan, Shuqiong ; Feng, Meixi ; He, Zhipeng ; Huang, Yong ; Jiang, Chenran ; Lian, Chenshan ; Kang, Wei ; Yang, Jinglei ; Liu, Zhihong ; Yin, Feng ; Wu, Yun-Dong ; Ye, Yuxin ; Song, Chunli ; Zhao, Juan

CDK4/6 inhibitors are effective in treating HR⁺/HER2^- breast cancer but face limitations due to therapeutic resistance and hematological toxicity, particularly from strong CDK6 inhibition. To address these challenges, designing selective inhibitors targeting specific cyclin-dependent kinases (CDK) members could offer clinical advantages and broaden CDK inhibitor indications. However, the highly conserved binding pockets of CDKs complicate selective targeting. This study leverages in silico modeling and structural analysis of cocrystal data to identify subtle differences in key CDK binding pockets. Notably, a sequence difference in the αD-helix motif between CDK4 and CDK6 provides a targetable "sweet spot" for selectivity. By incorporating a 1,4-trans-cyclohexanediamine side chain, we designed molecules that favor interactions with CDK4 over CDK6 and explored potential dual CDK4/9 inhibition. This approach yielded a lead compound with distinct in vitro selectivity and promising in vivo pharmacokinetics, offering valuable insights for the development of selective next-generation CDK inhibitors.

310

项与羟乙磺酸达尔西利相关的新闻（医药）

2025-07-27

·ioncology

2025年ESMO年会部分摘要题目公布，一文汇总当前入选的乳腺癌领域中国研究

点击蓝字，关注我们编者按：2025年欧洲肿瘤内科学会年会（ESMO 2025）将于10月17日至21日在德国柏林召开，作为肿瘤学界的年度盛典，ESMO每年都会吸引上万名世界各地的肿瘤学专家参与，为全球学者提供了良好的交流平台。目前，ESMO官网已公布了大会部分口头报告及壁报标题，肿瘤瞭望特将目前乳腺癌领域入选的中国学者投稿研究进行汇总，并诚邀您持续关注重磅研究进展！Breast cancer, early（早期乳腺癌）Mini oral session297MO-Timing of Pegfilgrastim Administration and Pegfilgrastim-Induced Bone Pain: A Prospective, Randomized Phase 3 Trial培非格司亭给药时机与培非格司亭诱导的骨痛：一项前瞻性随机III期试验讲者：Peiyong Li (Guangzhou, China)Posters and ePosters298P - Development and validation of a novel HER2RI assay for predicting the risk of recurrence and survival in Asian population with HER2-positive breast cancer用于预测亚洲HER2阳性乳腺癌患者复发和生存风险的新型HER2RI检测方法的开发和验证讲者：Yi-Kun Kang (Beijing, China)300P - TIME-HER: A Dynamic Predictive Model for Prognosis of HER2-Positive Early Breast Cancer after HER2-targeted TherapyTIME-HER：HER2靶向治疗后HER2阳性早期乳腺癌预后的动态预测模型讲者：Qingyao Shang (Beijing, China)305P - Neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer: three-year outcomes from the MUKDEN 01 studyMUKDEN 01研究三年随访结果：吡咯替尼联合来曲唑及达尔西利新辅助治疗三阳性乳腺癌的疗效分析讲者：刘彩刚 (Shenyang, China)306P - 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A modern DCIS-IBC guide board for postoperative upgrading in ductal carcinoma in situ导管原位癌术后升级为浸润性乳腺癌的现代风险评估指南框架讲者：Chenglong Duan (xian, China)383P - Spatial transcriptomics reveals biological disparities in ipsilateral breast tumor recurrence after breast-conserving surgery空间转录组学揭示保乳术后同侧乳腺肿瘤复发的生物学差异讲者：FEILIN QU (Shanghai, China)385P - Is axillary intervention necessary for selected patients with cN0-1 breast cancer after neoadjuvant chemotherapy?新辅助化疗后的cN0-1乳腺癌患者是否有必要进行腋窝干预？讲者：Yuhan Zhang (Xi'an, Shaanxi Province, China)386P - The Innovative Lancet Technique for Breast-Conserving Oncoplastic Surgery in Small- to Medium-Sized Breasts with Tumors in the Lower Inner Quadrant: A Multicenter Retrospective Study (IOS Study)针对中小乳房下内侧象限肿瘤的保乳整形手术创新Lancet技术：一项多中心回顾性研究（IOS研究）讲者：Rui Zhuo (Guilin, China)389P - A Competing Risk Analysis Model to Explore the Impact of Postoperative Radiotherapy for Sentinel Lymph Node Micrometastases or ITCs in Female Breast Cancer竞争风险分析模型探讨术后放疗对女性乳腺癌前哨淋巴结微转移或孤立肿瘤细胞（ITCs）的影响讲者：Yudong Zhou (xian, China)391P - Application of Preoperative 3-dimensional Vascular Reconstruction Assessment in Preventing Ischemic Complications After Nipple-Sparing Mastectomy: A Randomized Controlled Trial术前三维血管重建评估在预防保留乳头乳房切除术后缺血性并发症中的应用：一项随机对照试验讲者：Xiaoqi Zhang (Guangzhou, China)398P - Patient-reported outcomes (PROs) with GnRHa as ovarian function suppression (OFS) treatment in pre-menopausal Chinese patients with hormone receptor-positive (HR+) early breast cancer (EBC): a real-world observational investigationGnRHa作为卵巢功能抑制（OFS）治疗绝经前激素受体阳性（HR+）早期乳腺癌（EBC）患者的患者报告结局（PROs）：一项真实世界观察性研究讲者：Xiyu Liu (Shanghai, China)403P - Axillary Lymph Node Dissection Offers No Survival Benefit in Breast Cancer Patients with Sentinel Lymph Node Micrometastases After Neoadjuvant Therapy腋窝淋巴结清扫术对新辅助治疗后前哨淋巴结微转移的乳腺癌患者无生存获益讲者：Jianing Zhang (Xi'an, China)414P - Prognostic Value of ER reduction rate between pre- and post- Neoadjuvant Chemotherapy in Patients with ER-Positive/HER2-Negative Breast Cancer新辅助化疗前后ER降低率对ER阳性/ HER2阴性乳腺癌患者的预后价值讲者：Shunyi Liu (Fuzhou, China)416P - Diverse adjuvant treatment in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy: A single center real-world study新辅助化疗后残留病灶的三阴性乳腺癌患者的多样化辅助治疗：一项单中心真实世界研究讲者：Xi Chen (Beijing, China)417P - Proteomic analysis of residual disease identifies potential prognostic biomarkers of triple-negative breast cancer after neoadjuvant chemotherapy三阴性乳腺癌新辅助化疗后残留病灶的蛋白质组学分析确定潜在的预后生物标志物讲者：Xi Chen (Beijing, China)418P - Impact of BRCAness Status on Prognosis and Chemotherapy Sensitivity in Non-pCR Triple-Negative Breast Cancer Patients After Neoadjuvant TreatmentBRCA样状态对新辅助治疗后未达病理完全缓解（non-pCR）三阴性乳腺癌患者预后及化疗敏感性的影响讲者：Hangcheng Xu (Beijing, China)429eP - Identification of Low Risk Patients with ER+/HER2- Breast Cancer by mRNA-based LRP Model通过基于mRNA的LRP模型识别ER+/HER2-乳腺癌的低危患者讲者：梁旭 (Beijing, China)430eP - Peri-lymph node tattooing with carbon nanoparticles suspension: a novel strategy for targeted axillary dissection in breast cancer纳米碳混悬标记淋巴结周围：一种乳腺癌靶向腋窝清扫的创新策略讲者：Junyuan Lv (Zunyi, China)436eP - 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H4K8la/CXCL10-driven M2 polarization via tumor cell-macrophage lactate feedback loop mediates doxorubicin resistance in TNBCH4K8la/CXCL10通过肿瘤细胞-巨噬细胞乳酸反馈回路驱动M2型巨噬细胞极化，介导三阴性乳腺癌对多柔比星的耐药性讲者：Qingqing Wang (Wuhan, China)（来源：《肿瘤瞭望》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。

临床2期临床结果

2025-07-14

·ioncology

宋传贵教授：ASCO年会乳腺癌新辅助治疗——聚焦升阶梯与降阶梯治疗新进展与未来发展趋势

点击上方蓝字关注我们编者按：由广东省预防医学会主办，广东省人民医院协办的2025广东省预防医学会乳腺癌防治专业委员会学术研讨会日前于广州圆满落幕。复旦大学附属肿瘤医院福建医院（福建省肿瘤医院）宋传贵教授在本次会议上带来了“2025 ASCO乳腺癌新辅助治疗进展”的讲课，会后，肿瘤瞭望特邀采访了宋传贵教授，请他就2025年ASCO年会新辅助治疗研究的整体趋势及相关进展进行了介绍。01《肿瘤瞭望》：2025年ASCO年会中，乳腺癌新辅助治疗领域有多项突破性研究成果公布，尤其是降阶梯治疗、靶向联合方案等议题备受关注。王坤教授公布的neoCARHP研究结果显示，THP方案在HER2阳性早期乳腺癌治疗中达到非劣效于含卡铂（TCbHP）方案的pCR率，且安全性更优。您如何评价这一结果对临床实践的影响？作为国内乳腺癌领域专家，请您为我们总结下2025年ASCO年会新辅助治疗研究的整体趋势。宋传贵教授复旦大学附属肿瘤医院福建医院（福建省肿瘤医院）众所周知，HER2阳性早期乳腺癌新辅助治疗，已经形成了靶向联合化疗的治疗模式。目前，HER2阳性早期乳腺癌患者新辅助治疗的pCR率可以达到60%甚至更高，但当今临床治疗的关键点在于，如何减轻乳腺癌患者药物治疗带来的毒性，同时保持治疗疗效。广东省人民医院王坤教授在2025年ASCO大会带来了HER2阳性早期乳腺癌新辅助治疗的neoCARHP研究，结果显示，THP方案pCR率非劣效于TCbHP方案（64.1% vs 65.9%）。目前来看，对于铂类添加与否，临床一直存在争议，最近公布的多项临床研究也证实，“去铂类”其实并不影响患者整体的pCR率，同时又能减少铂类带来的血液学和消化道等不良反应。△neoCARHP研究pCR率未来，对于HER2阳性乳腺癌的新辅助治疗，更多的是朝着“降阶梯”治疗的方向发展，无论是“去铂类”还是缩短新辅助治疗的疗程（降低治疗强度），甚至未来可能实现应用单一的ADC药物来代替现有的三药/四药联合治疗方案，以上这些均代表了未来以更少的药物来争取相似或者更好的治疗疗效，同时减少多药化疗引起的不良反应的发展趋势。目前新辅助治疗研究不止于此。尽管现在许多新辅助治疗研究仍以pCR为主要研究终点，但可以看到一个趋势，即大家越来越关注长期生存，因此很多研究以iDFS甚至OS作为主要研究终点，这类研究更能体现我们对乳腺癌患者全程治疗的关注。当前的临床研究多聚焦于ADC药物，由此可见，我们对ADC药物治疗还是充满期待的。复旦大学附属肿瘤医院李俊杰教授在2024年SABCS大会上报告的FASCINATE-N研究结果显示，SHR-A1811单药治疗HER2阳性早期乳腺癌的疗效与多药联合取得的pCR率相当。未来，他们还会进行更长时间随访，若能证明SHR-A1811单药对长期预后的结果相似，或将改变当前临床实践。当然，目前我们不能简单认为一项或少数几项研究数据就能改变当前临床实践，因为需要根据研究中的入组人群进一步区分。若“去卡铂”药物方案可行，目前可能仅在相对早期患者中试用，想要大规模运用可能还需等待时机，但这至少也是“降阶梯”治疗进步的表现。此外，今年ASCO年会上WSG的联合分析等研究数据公布，也体现了这一趋势，让我们对目前新辅助治疗的理解更进一步。02《肿瘤瞭望》：DAWNA-A研究证实，达尔西利联合内分泌治疗可显著改善HR+/HER2-高危早期乳腺癌患者的无浸润性疾病生存期（iDFS）。您如何看待CDK4/6抑制剂从晚期治疗向辅助治疗的延伸？宋传贵教授复旦大学附属肿瘤医院福建医院（福建省肿瘤医院）事实上，对于乳腺癌患者的治疗，不同分子亚型患者所运用的治疗策略是不一样的，一些患者需要进行“降阶梯”治疗，而另一些患者则需要“升阶梯”治疗。如对于HR+乳腺癌患者，我们是否需要在传统内分泌治疗的基础上进行“加码”？现在多项相关研究结果的公布，也使患者的治疗之路越来越清晰，治疗选择也越来越多样化。以高危HR+早期乳腺癌患者治疗为例，这类患者的复发风险主要存在于第二个5年，我们不仅要强调对于绝经前或者围绝经期患者的卵巢功能抑制，同时也会在患者内分泌治疗强度和时间上给予相应调整。如对于早期高危患者我们会在OFS+内分泌基础上联合CDK4/6抑制剂或者适当延长患者内分泌治疗的时间（内分泌治疗时间可延长至10年）。从monarchE研究到NATELEE研究，再到2025年ASCO年会上邵志敏教授报道的DAWNA-A研究，均证明了CDK4/6抑制剂联合内分泌治疗能使乳腺癌患者的生存期延长。DAWNA-A研究更是基于中国患者人群数据，入组了超过5000例患者的数据，结果证实，达尔西利+内分泌治疗相较于安慰剂+内分泌治疗有更多的生存获益（2年iDFS达尔西利组94.7% vs安慰剂组90.2%，HR=0.56（0.43-0.71），P＜0.0001）。△DAWNA-A研究iDFSCDK4/6抑制剂在HR+早期乳腺癌患者治疗中的适应症获批，对于早期高危乳腺癌患者而言，治疗选择增多的同时，也能使其复发和转移风险下降，能为患者争取更多的治疗希望和治愈空间。因此，我们对DAWNA-A研究也充满了更多期待。宋传贵教授复旦大学附属肿瘤医院福建医院（福建省肿瘤医院）主任医师、教授、博士生导师乳腺肿瘤学科带头人/乳腺肿瘤诊治中心执行主任中国抗癌协会乳腺癌专业委员会常委中国抗癌协会肿瘤靶向治疗专委会常委福建省抗癌协会乳腺癌专业委员会主任委员中华医学会肿瘤分会乳腺肿瘤学组成员CSCO乳腺癌专家委员会委员（来源：《肿瘤瞭望》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。

ASCO会议抗体药物偶联物临床结果临床1期

2025-07-10

·CPHI制药在线

正大天晴库莫西利申报新适应症，剑指HR+/HER2-乳腺癌一线治疗

关注并星标CPHI制药在线7月9日，正大天晴递交的库莫西利胶囊和氟维司群注射液的上市申请获CDE受理，笔者推测此次申报的适应症为：库莫西利联合氟维司群治疗既往未经治疗的激素受体(HR)阳性、人表皮生长因子受体2(HER2)阴性局部晚期或转移性乳腺癌。库莫西利是正大天晴研发的一种新型周期蛋白依赖性激酶2、4和6(CDK2/4/6)抑制剂，对CDK2、CDK4、CDK6激酶有不同程度的抑制效果。研究结果显示：与阿贝西利相比，库莫西利对CDK2的抑制作用进一步提升，其增强的CDK2和CDK4抑制活性可能有助于在临床上克服目前CDK4/6抑制剂的耐药性问题。2024年7月，库莫西利联合氟维司群用于既往内分泌经治的HR阳性、HER2阴性局部晚期或转移性乳腺癌适应症的上市申请获CDE受理，相关受理号为：CXHS2400055/56。此次库莫西利申报新适应症是基于3期临床试验TQB3616-III-02(NCT04523272))的积极结果。该试验是国内首个CDK2/4/6抑制剂联合氟维司群用于晚期乳腺癌一线治疗的关键3期研究。结果显示：库莫西利联合氟维司群可显著降低晚期一线乳腺癌患者的疾病进展或死亡风险，主要终点达到统计学差异，且有临床意义，且联合方案总体安全可耐受。HR+/HER2-乳腺癌是最常见的乳腺癌亚型，约占所有乳腺癌的70%。CDK4/6抑制剂的出现改变HR+/HER2-乳腺癌传统内分泌治疗的格局，开启了内分泌治疗联合靶向治疗的精准时代。据不完全统计，目前国内已批准9款CDK4/6抑制剂，详见下图。除了曲拉西利被批准用于化疗引起的骨髓抑制，另外8款均被批准用于治疗HR+/HER2-乳腺癌，而且哌柏西利、瑞波西利、阿贝西利、达尔西利和来罗西利均已被批准用于HR+/HER2-乳腺癌的一线治疗。值得一提的是，近年来国产CDK4/6抑制剂崛起，其中达尔西利、吡洛西利、伐维西利和泰瑞西利均由国内药企研发。随着CDK4/6抑制剂的广泛应用，其耐药问题也逐渐引发关注。研究发现，在CDK4被抑制后，CDK2会接管其作用并促进癌细胞增殖，而且这些癌细胞还可能对之前的CDK抑制剂治疗产生耐药。这表明CDK2可能是CDK4/6耐药机制之一。CDK2抑制剂的开发被认为是破局CDK4/6抑制剂耐药的方向之一。据不完全统计，国内外已有多家药企研发了CDK2抑制剂，如锐格医药、辰欣药业、同源康医药。锐格医药开发了两款CDK2抑制剂，其中RGT-419B是一款CDK2/4/6/抑制剂，处于1期临床。临床前数据显示：在对已批准的CDK4/6抑制剂耐药的ER+乳腺癌细胞中，RGT-419B显示出对癌细胞增殖的完全抑制。而且，在试验中RGT-419B与SERD或PI3K信号通路抑制剂联用时，对肿瘤细胞的抑制作用进一步增强。QR-6401是一款CDK2抑制剂，处于临床前阶段。同源康医药也开发了两款CDK2抑制剂，其中TY-0540是一种选择性CDK2/4/6抑制剂，在对小鼠模型进行的临床前研究中，其在高达40mg/kg（BID）表现出优异的耐受性及于此剂量水平表现出对乳腺癌和胰腺癌的初步疗效。TY-1210是一种选择性CDK2抑制剂，处于临床前阶段。整体来看，正大天晴的库莫西利是进展最快的CDK2/4/6/抑制剂，不过适应症未涉及CDK4/6/抑制剂耐药乳腺癌。此外，围绕CDK2抑制剂，多家药企已达成合成：2023年11月，百济神州与昂胜医药达成一项授权合作，从后者引进一款CDK2抑制剂ETX-197，交易总交易额达13.3亿美元；2024年10月，罗氏与锐格医药就下一代CDK抑制剂达成收购协议，据协议罗氏将以8.5亿美元的首付款收购锐格医药的下一代CDK抑制剂。END智药研习社近期直播预告来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

临床3期申请上市

100 项与羟乙磺酸达尔西利相关的药物交易

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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
HR阳性/HER2阴性乳腺癌	中国	江苏恒瑞医药股份有限公司	2021-12-31

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10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
去势敏感前列腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2023-10-19
HER2 阴性乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2021-04-30
HR阳性乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2021-04-30
淋巴结阳性乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2021-04-30
晚期乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2019-06-13
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2019-06-13
转移性去势抵抗性前列腺癌	临床2期	中国	江苏恒瑞医药股份有限公司	2024-07-31
ER阳性/HER2阴性乳腺癌	临床2期	中国	山东盛迪医药有限公司	2023-12-20
尤文肉瘤	临床2期	中国	江苏恒瑞医药股份有限公司	2023-07-01
转移性软组织肉瘤	临床2期	中国	江苏恒瑞医药股份有限公司	2023-07-01

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临床结果

适应症

分期

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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


NCT05586841 (ASCO2025) 人工标引	临床1期	HR阳性/HER2阴性乳腺癌 HER2 Negative \| Hormone Receptor Positive	22	dalpiciclib + chidamide	鏇鹹餘顧衊糧膚鏇膚積(夢願齋鑰糧夢窪壓積繭) = the MTD was established as Group C (dalpiciclib 100 mg/d, chidamide 25 mg BIW). 齋鹽廠範衊鬱觸鏇鹹鹹 (醖襯繭鹽蓋簾簾鬱網糧 )	积极	2025-05-30
				dalpicicldalpiciclibchidamide (Group C: dalpiciclib 100 mg/d, chidamide 25 mg BIW)
NCT06495515 (ASCO2025)	临床2期	HR阳性HER2阴性淋巴结阳性乳腺癌一线 HR+ \| HER2-negative	26	Dalpiciclib plus Toremifene	艱觸觸憲衊襯獵積淵網(艱顧鬱鏇鏇築積簾遞醖) = 憲網顧簾顧膚餘顧鑰艱鹽網製壓壓廠窪鏇膚窪 (鹹糧積衊願鬱顧憲夢襯 ) 更多	积极	2025-05-30
NCT05806671 (Bayesian optimal phase Ⅱ trial, ASCO2025)	临床2期	HR阳性/HER2低表达乳腺癌	30	Dalpiciclib plus Fulvestrant and Pyrotinib	繭衊窪憲淵齋製壓衊製(簾構鹽顧夢築簾選齋願) = 衊壓醖淵窪憲糧觸醖築憲獵觸構願範蓋顧膚糧 (膚夢觸蓋顧鹽醖鏇鬱繭 ) 更多	积极	2025-05-30
				Abemaciclib	壓顧網廠繭網膚簾構艱(窪鑰築鬱鹹膚艱餘鬱構) = 膚鹹積襯窪衊壓齋餘糧簾憲襯鏇鹽顧獵醖餘築 (顧顧糧餘醖製膚壓襯鑰, 1.1 ~ 5.1)
NCT04842617 (DAWNA-A, ASCO2025)	临床3期	早期乳腺癌辅助 HR+ \| HER2-	5,274	Dalpiciclib (Dalp) + Endocrine Therapy (ET)	積淵糧壓繭窪襯廠觸鏇(築鏇積鹽淵齋鹹餘構網): HR = 0.56 (95% CI, 0.43 ~ 0.71)	积极	2025-05-30
				Placebo + Endocrine Therapy (ET)
NCT05640778 (DANCER, ASCO2025)	临床2期	HER2 阴性乳腺癌新辅助 ctDNA clearance \| Olink proteomic analyses \| somatic variation profiling ... 更多	30	dalpiciclib (Good Responders (GR))	憲鹹膚鑰餘窪窪齋廠範(簾積築糧觸廠構糧蓋壓) = significant shift in copy number pattern after treatment at S 糧壓製膚簾遞夢壓觸觸 (鬱鬱鬱積壓繭壓鬱壓衊 )	积极	2025-05-30
				dalpiciclib (Moderate Responders (MR))
CTR20210652 (DAWNA-A \| SHR6390-III-303, NEWS) 人工标引	临床3期	HR阳性/HER2阴性乳腺癌 HER2 Negative \| Hormone Receptor Positive	5,000	羟乙磺酸达尔西利+内分泌治疗	鬱鏇齋襯壓艱衊繭齋衊(觸齋淵襯蓋餘糧憲憲築) = 达尔西利联合内分泌治疗，较安慰剂联合内分泌治疗，可显著降低患者复发风险，提高患者无侵袭性疾病生存期醖餘顧願顧築製餘窪壓 (蓋襯鹽衊壓齋壓獵鬱遞 ) 达到	积极	2025-02-23
				安慰剂+内分泌治疗
NCT05512780 (DARLING 01, Pubmed \| Breast Cancer Res) 人工标引	临床2期	HR阳性/HER2阴性乳腺癌新辅助 HER2 Negative \| Hormone Receptor Positive	29	Dalpiciclib + Letrozole	醖糧憲範衊壓鹹製積廠(顧選選繭獵簾淵積製積) = 鹹蓋積膚積廠夢選壓艱窪齋淵糧鑰獵選鑰夢夢 (齋簾齋齋艱鏇醖鬱窪鬱 ) 更多	积极	2025-02-13
NCT03966898 (DAWNA-2, SABCS2024) 人工标引	临床3期	HR阳性/HER2阴性乳腺癌一线 Hormone Receptor Positive \| HER2 Negative	456	Dalpiciclib + Letrozole/Anastrozole	顧鹹簾淵鹽廠壓壓遞鏇(鏇簾築蓋構夢鑰選夢遞) = 構壓鬱鬱壓醖製壓鏇繭蓋糧鏇齋餘窪遞築糧鏇 (鏇醖糧壓糧築蓋膚簾齋, 29.6 ~ 39.0) 更多	积极	2024-12-12
				Placebo + Letrozole/Anastrozole	顧鹹簾淵鹽廠壓壓遞鏇(鏇簾築蓋構夢鑰選夢遞) = 醖鹹膚糧衊構醖獵遞觸蓋糧鏇齋餘窪遞築糧鏇 (鏇醖糧壓糧築蓋膚簾齋, 16.5 ~ 22.5) 更多
NCT05431504 (SABCS2024 \| NEWS) 人工标引	临床2期	HR阳性/HER2阴性乳腺癌 Hormone Receptor Positive \| HER2 Negative	53	Dalpiciclib plus ET	艱遞鏇遞選蓋糧鹽鬱窪(製範鹽獵網餘淵鹹壓膚) = 願築窪壓壓糧簾繭膚淵憲蓋夢淵鏇積夢窪艱膚 (壓廠壓襯繭窪選鹽鑰糧, 7.59 ~ NE) 更多	积极	2024-11-26
				Chemotherapy (external control group)	艱遞鏇遞選蓋糧鹽鬱窪(製範鹽獵網餘淵鹹壓膚) = 顧觸製鏇築築艱醖遞廠憲蓋夢淵鏇積夢窪艱膚 (壓廠壓襯繭窪選鹽鑰糧, 2.92 ~ 5.91) 更多
NCT06009627 (ESMO2024) 人工标引	临床2期	绝经前乳腺癌新辅助 HER2 Negative \| Hormone Receptor Positive	32	Dalpiciclib, Exemestane, and Goserelin	願鏇鑰糧窪顧鑰餘窪膚(構壓壓觸願糧憲齋範糧) = 積選夢獵糧觸淵壓範獵膚繭範醖窪觸衊範艱壓 (範獵鏇顧襯膚鹹築築醖 )	积极	2024-09-16
				TAC (docetaxel, doxorubicin, and cyclophosphamide)	願鏇鑰糧窪顧鑰餘窪膚(構壓壓觸願糧憲齋範糧) = 膚繭選淵憲獵蓋製築壓膚繭範醖窪觸衊範艱壓 (範獵鏇顧襯膚鹹築築醖 )