VIKTORIA-2: A Randomized, Open-Label, Phase 3 Study of Fulvestrant and CDK4/6 Inhibitors With or Without Gedatolisib as First-Line Treatment in Patients With HR-Positive and HER2-Negative Advanced Breast Cancer

This is a Phase 3, open-label, randomized, clinical trial evaluating the efficacy and safety of gedatolisib plus fulvestrant and CDK4/6 Inhibitors for the treatment of patients with locally advanced or metastatic HR+/HER2- advanced breast cancer.

开始日期2025-06-30

申办/合作机构

Celcuity, Inc.

NCT06753747

/ Not yet recruiting临床1/2期IIT

A Phase 1b/2 Trial of Afatinib Plus Palbociclib in Previously Treated Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

The goal of this clinical trial is to learn if Afatinib plus Palbociclib works in previously treated recurrent or metastatic esophageal squamous cell carcinoma. It will also learn about the safety of the combination of Afatinib and Palbociclib. The main questions it aims to answer are:
What is the safe and tolerable dose of Afatinib when combined with 100 mg of Palbociclib (administered orally, three weeks on and one week off)?
Does the combination therapy of Afatinib and Palbociclib induce a tumor response in patients with recurrent or metastatic esophageal squamous cell carcinoma who have received prior treatments?

开始日期2025-04-01

申办/合作机构

四川大学华西医院（四川省国际医院）

NCT06757335

/ Not yet recruiting临床1/2期

A Multicenter, Open, Dose Escalation/dose Escalation, and Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Oral HP568 Tablets Alone and in Combination with Palbociclib in Patients with ER+/HER2 Advanced Breast Cancer

This is a Phase 1/2 dose escalation and cohort expansion study and will assess the safety, tolerability and preliminary efficacy of HP568 alone and in combination with palbociclib in patients with ER+/HER2- locally advanced or metastatic breast cancer.

开始日期2025-01-07

申办/合作机构

海创药业股份有限公司

100 项与哌柏西利相关的临床结果

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100 项与哌柏西利相关的转化医学

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100 项与哌柏西利相关的专利（医药）

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2,150

项与哌柏西利相关的文献（医药）

2025-03-01·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Three sample preparation methods for clinical determination of CDK4/6 inhibitors with endocrine therapy in breast cancer patient plasma using LC-MS: Cross-validation (red), ecological (green) and economical (blue) assessment

Article

作者: Mlinarić, Zvonimir ; Turković, Lu ; Sertić, Miranda ; Lovrić, Mila ; Silovski, Tajana ; Nigović, Biljana

Cyclin D-dependent kinase 4/6 inhibitors palbociclib, ribociclib and abemaciclib, in combination with aromatase inhibitors anastrozole and letrozole or oestrogen receptor degrader fulvestrant, are being assessed as candidates for therapeutic drug monitoring. An ideal bioanalytical method for their determination in patient plasma samples is therefore of high interest, as there is no routine reference method yet available in the clinical practice. In this work, three sample preparation approaches - dispersive liquid-liquid microextraction (DLLME), solid-phase extraction (SPE), and newly developed phospholipid removal (PLR) for LC-MS determination of these six drugs are comprehensively assessed. The methods are validated in the clinically relevant linear ranges with remarkable precision (RSD ≤6.9 %) and accuracy (bias -13.6 - 11.8 %). To compare the procedures in a real-world setting, they are applied on 38 samples from breast cancer patients. The differences between paired results are below 20 % for more than 92 % of the repeats and the RSD is ≤13.1 % between the corresponding results. Statistical comparison of the results reveals excellent overall agreement between the methods (Lin's concordance correlation coefficient ≥0.9969, maximal Bland-Altman bias 6.3 %). DLLME proved to be the most ecologically acceptable method due to the high degree of miniaturisation (AGREEprep score 0.44), PLR enabled very high sample throughput and cost-effectiveness (BAGI 72.5), while SPE showed the best analytical performance (redness score 100). All three methods are suitable for their designated purpose, and the choice of the ideal method can be made based on the scope of application, available funds and equipment and desired ecological footprint.

2025-02-01·BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Enhanced radiotherapy susceptibility in NSCLC through palbociclib-mediated PP5 inhibition

Article

作者: Chen, Grace ; Wang, Cheng-Yi ; Huang, Chao-Yuan ; Chen, Li-Ju ; Hong, Shiao-Ya

Radiotherapy remains a cornerstone in the treatment of non-small cell lung cancer (NSCLC), yet radioresistance often limits its efficacy. Identifying molecular targets that enhance radiosensitivity is crucial to offering both curative and palliative benefits for patients with NSCLC. Utilizing bioinformatics analysis, our study revealed significantly higher expression of PP5 in NSCLC tissues compared to normal tissues. Kaplan-Meier survival analysis also showed that high PP5 expression correlates with poorer overall survival, particularly in patients undergoing radiotherapy, suggesting a role for PP5 in radioresistance. We further demonstrated that PP5 is a critical target of palbociclib, distinct from CDK4/6, influencing radiosensitivity in NSCLC. Palbociclib enhanced radiotherapy susceptibility by inducing sustained DNA damage and AMPK activation. The subsequent cellular event is apoptosis rather than autophagy. Furthermore, the enhanced efficacy of combination therapy was counteracted by an AMPK inhibitor and PP5 activator, underscoring the importance of these pathways in mediating the response. Our findings provide compelling evidence that targeting PP5 can significantly enhance the therapeutic outcomes of radiotherapy in NSCLC. This research offers valuable insights into new combination therapy strategies, highlighting the potential of PP5 as a novel therapeutic target to overcome radioresistance.

2025-02-01·CURRENT MEDICINAL CHEMISTRY

A Molecular Dynamic Simulation, Structural Analysis, and Ex Vivo Insights into the P-glycoprotein Mediated Interactions of Dietary Polyphenols with Cyclin-dependent Kinase Inhibitors: A Potential Strategy to Counteract Drug Efflux

Article

作者: Dengale, Swapnil Jayant ; Channabasavaiah, Jagadish Puralae ; Anand, Vullendula Sai Krishna ; Ray, Rajdeep ; Patil, Prajakta Harish ; Bhat, Krishnamurthy ; Desai, Mrunal Pradeep ; Shenoy, G. Gautham

Introduction::

P-glycoprotein, an ATP-dependent efflux transporter, plays a crucial role in eliminating cellular toxins and affects the intracellular concentration and bioavailability of CDK 4/6 inhibitors. Moreover, dietary flavonoids are natural bio-enhancers that can effectively inhibit the efflux function of these transporters. Therefore, this study aimed to assess the impact of dietary polyphenols on the inhibition of P-glycoprotein and the subsequent efflux of CDK inhibitors palbociclib and ribociclib.

Methods::

A molecular docking approach was implemented to evaluate the binding interaction characteristics of CDK4/6 inhibitors in the presence of dietary polyphenols at the ATP binding site. Furthermore, the stability of the complexes was evaluated in two conformations of P-glycoprotein, followed by an ex vivo everted gut sac experiment.

Results::

The findings demonstrated that the binding of curcumin and quercetin with high affinity (-51.63 and -47.16 Kcal/mol) to ATP binding sites of P-glycoprotein-palbociclib and ribociclib inward conformation complexes resulted in good stability of complex and minimal fluctuation throughout the course of the simulation. It was evident from the everted gut sac ex vivo study that the presence of 100 μM of curcumin resulted in an increase of 1.77 and 4.20-fold in the intestinal transit of palbociclib and ribociclib, respectively.

Conclusion::

The study emphasizes the significance of curcumin and quercetin as inhibitors of P-glycoprotein, demonstrating their potential to decrease the efflux of palbociclib and ribociclib, consequently contributing to their bioavailability enhancement.

999

项与哌柏西利相关的新闻（医药）

2025-01-22

·ioncology

张清媛教授：HDACi精准调控表观遗传，为HR+晚期乳腺癌患者带来更多治疗选择

点击蓝字，关注我们编者按：组蛋白去乙酰化酶（HDAC）是调控表观遗传学改变的组蛋白修饰酶，与乳腺癌的发生发展以及耐药密切相关。HDAC抑制剂（HDACi）可靶向性调控表观遗传学特征，从而控制肿瘤细胞增殖、调节肿瘤细胞周期及修复DNA损伤，是当前调控表观遗传学抗肿瘤治疗的典型代表，也是我国指南推荐的HR+/HER2-晚期乳腺癌内分泌耐药后的重要治疗选择。本文特邀哈尔滨医科大学附属肿瘤医院张清媛教授为我们分析当前HR+/HER2-晚期乳腺癌患者的治疗现状，从而进一步梳理HR+/HER2-晚期乳腺癌内分泌耐药后的可选治疗方案。 HR+晚期乳腺癌一线CDK4/6i＋ET进展后如何“续航” HR+乳腺癌是最常见的乳腺癌分子亚型，约占总体乳腺癌的70%，在患者数量上代表了最为广泛的临床治疗需求。针对晚期HR+乳腺癌，目前CDK4/6抑制剂联合内分泌治疗（CDK4/6i＋ET）已经成为标准一线治疗，可使患者的中位无进展生存期（PFS）延长至2年以上，中位总生存期（OS）延长至5年以上[1]。然而，CDK4/6i＋ET治疗进展后的患者，目前尚无治疗标准，不同治疗方案均有一定的局限性：（1）对于化疗，仅能带来3-4个月的PFS，而且化疗毒副作用大、治疗耐受性差[2-4]。（2）对于CDK4/6i跨线治疗，虽然部分研究结果提示有一定程度的获益，但总体上的证据有限，需谨慎选择[5]。目前获阳性结果的3期研究仅有一项（postMONARCH研究），且CDK4/6i跨线组与对照组的PFS仅有0.7个月的微弱改善（6.0 vs 5.3个月，HR 0.73；P=0.02）[6]。（3）另一大类的后线治疗是基于生物标志物选择的靶向治疗或新型内分泌治疗，但这些治疗仅限于PI3K/AKT/mTOR通路（PAM通路）、ESR1、BRCA等突变人群中，而且目前临床实践中的基因检测仍存在标准不统一、可及性不足、经济负担大等挑战。因此，临床亟需为CDK4/6i＋ET失败患者提供更多生存“续航”的治疗方案，既要关注治疗方案的有效性和安全性，也要关注其可及性、可负担性和便捷性。表观遗传调控抗肿瘤新药研发的“热门赛道” 有别于基因突变，表观遗传是在不改变DNA序列的前提下，机体通过DNA甲基化、乙酰化、染色质重构、非编码RNA等机制，引起可遗传的基因表达变化或表型改变；某些基因突变也可导致表观调控异常。对中国乳腺癌中常见突变基因和肿瘤突变负荷（TMB）特征的研究[7]显示，我国乳腺癌患者存在KMT2C、ARID1A、KAT6A、CREBBP、KDM5A等众多表观遗传因子的异常，针对表观遗传调控的抗肿瘤治疗策略蕴藏着较大的潜力。 2004年，FDA正式批准了全球第一款表观遗传学抗肿瘤药物阿扎胞苷（Azacitidine），用于治疗骨髓增生异常综合征（MDS）。此后的二十年间，随着抗肿瘤表观遗传学研究不断深入而涌现了多种新型靶点药物，较为常见的作用蛋白主要集中在DNA甲基转移酶（DNMT）、组蛋白去乙酰化酶（HDAC）、异柠檬酸脱氢酶（IDH）、Zeste 增强子同源物（EZH）[8]。其中，乳腺癌的表观遗传抗肿瘤药物研究最为丰富，一项对美国临床试验注册网站ClinicalTrials.gov进行乳腺癌表观遗传学试验的横断面研究显示，在涉及22种表观遗传学抗肿瘤药物的100个临床试验中，有38个是针对乳腺癌的临床试验，其中HDACi是被研究最多的体外药物，占总数的45.45%[9]。 HDAC抑制剂延缓内分泌耐药组蛋白去乙酰化酶（HDAC）是一类影响肿瘤表观遗传学改变的关键修饰酶，参与肿瘤细胞生长与表达调控等诸多过程，是目前乳腺癌表观遗传学抗肿瘤药物设计中最常见的靶点之一[10]。组蛋白乙酰化和去乙酰化的失衡与乳腺癌的发生发展密切相关，一项基于300例乳腺浸润性导管癌患者的组织芯片研究发现，有42.3%～73.0%的患者高表达HDAC1、HDAC2、HDAC4或HDAC6，且HDAC1和HDAC6与HR+乳腺癌较长的OS相关[11]；另一项分析24例乳腺癌的研究显示，有75%的癌组织HDAC1 mRNA水平高于癌旁组织[12]。除了广泛存在的HDAC表达以外，HDAC还与多种乳腺癌内分泌治疗耐药模式息息相关，在CDK4/6i的细胞周期特异性耐药机制中也存在广泛的联系。例如，p21表达缺失是CDK4/6i的耐药机制之一，HDAC抑制剂（HDACi）可直接激活p21或通过激活p53而上调p21表达，进而诱导乳腺癌多药耐药细胞周期阻滞和细胞凋亡，从而逆转CDK4/6i耐药[13-15]。此外，HDACi还可以上调PTEN水平，从而抑制PAM信号通路所导致的内分泌或CDK4/6i耐药[16]。 △HDACi逆转CDK4/6i耐药机制示意图（图源[13]）由此可见，HDAC广泛参与乳腺癌内分泌治疗和细胞周期治疗的相关耐药机制，抑制HDAC是延缓内分泌治疗和CDK4/6i耐药的重要策略。恩替司他落地为乳腺癌患者提供更多选择恩替司他于2024年4月获中国NMPA批准联合AI用于经内分泌治疗复发或进展的局部晚期或转移性HR+/HER2-乳腺癌患者治疗，标志着恩替司他正式进入中国临床实践。恩替司他的获批主要基于中国3期临床试验（EOC103A3101）[17]所取得的积极结果。该研究入组经内分泌（辅助或解救）治疗复发或进展的局晚期或转移性HR+/HER2-乳腺癌患者，随机接受恩替司他或安慰剂联合依西美坦治疗。研究结果显示达到主要终点，恩替司他组经独立评审中心（IRC）评估的中位无进展期（PFS）相较于对照组延长近1倍，风险显著降低24%（6.32 vs 3.72个月，HR 0.76，95%CI：0.58～0.98，P=0.046），各个亚组的获益趋势保持一致。在经CDK4/6i治疗的患者中，恩替司他组的PFS事件风险显著降低43%（HR 0.57），经解救化疗的患者PFS事件风险则降低29%（HR 0.71）。在次要终点方面，恩替司他的总生存期（OS）长达38.39个月，是目前HDACi同类3期研究中取得的最长OS，相较于对照组的死亡风险降低17%（HR 0.83）。 △EOC103A3101研究：IRC评估的PFS K-M曲线在安全性方面，恩替司他常见的≥3级血液学不良事件为中性粒细胞减少症（43.8%）、血小板减少症（8.5%）和白细胞减少症（6.4%），这些不良事件的发生率在数值上低于既往HDACi报道的发生率[18]；此外，恩替司他最常见≥3级非血液学治疗相关不良事件是天门冬氨酸氨基转移酶（AST）升高（2.6%）。另外一个值得关注的特点是，恩替司他的平均消除半衰期长达61.9小时[19]，采用的1周1次口服方案，这是目前乳腺癌抗肿瘤治疗药物中首个应用于临床的口服周疗方案，用药间隔的延长可以大大提高患者的治疗依从性。总之，表观遗传学普遍存在于乳腺癌患者中，对肿瘤的发生发展发挥重要作用；精准调控表观遗传学的治疗策略已经成为乳腺癌抗肿瘤药物的研发新热点。恩替司他作为原创的HDAC抑制剂，是精准调控表观遗传学抗肿瘤治疗的典型代表。3期临床试验已经证实其可以为患者带来显著的PFS获益以及超过38个月的OS，且血液学毒性较既往HDACi更低。此外，恩替司他为乳腺癌首个周疗口服的新型靶向治疗方案，用药方便。这些药物优势使得恩替司他可以极大的丰富临床治疗选择。张清媛教授主任医师、二级教授、博士生导师肿瘤学国家重点专科带头人国家百千万人才工程入选者国家突出贡献中青年专家中国抗癌协会淋巴瘤专业委员会主任委员中国抗癌协会乳腺癌专业委员会副主任委员中国临床肿瘤学会乳腺癌专家委员会副主任委员中国抗癌协会化疗专业委员会副主任委员参考文献：（滑动查看） [1]Guo X, Zhou Y, Zhang K, et al. First-line CDK4/6 inhibitor-based combinations for HR+/HER2- advanced breast cancer: A Bayesian network meta-analysis. J Evid Based Med. 2024;17(1):106-118. doi:10.1111/jebm.12571 [2]Kaufman PA, Awada A, Twelves C, et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015;33(6):594-601. doi:10.1200/JCO.2013.52.4892 [3]Li Y, Li W, Gong C, et al. A multicenter analysis of treatment patterns and clinical outcomes of subsequent therapies after progression on palbociclib in HR+/HER2- metastatic breast cancer. Ther Adv Med Oncol. 2021;13:17588359211022890. Published 2021 Jun 11. doi:10.1177/17588359211022890 [4]Ingrand I, Defossez G, Lafay-Chebassier C, et al. Serious adverse effects occurring after chemotherapy: A general cancer registry-based incidence survey. Br J Clin Pharmacol. 2020;86(4):711-722. doi:10.1111/bcp.14159 [5]Kalinsky K, et al. A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor–positive (HR+), HER2-negative metastatic breast cancer (MBC): MAINTAIN trial.2022 ASCO abstract LBA 1004 [6]Kevin Kalinsky, et al.postMONARCH: A phase 3 study of abemaciclib plus fulvestrant versus placebo plus fulvestrant in patients with HR+, HER2-, metastatic breast cancer following progression on a CDK4 & 6 inhibitor and endocrine therapy.J Clin Oncol 42, 2024 (suppl 17; abstr LBA1001) [7]Xiao W, Zhang G, Chen B, et al. Characterization of Frequently Mutated Cancer Genes and Tumor Mutation Burden in Chinese Breast Cancer. Front Oncol. 2021;11:618767. Published 2021 Apr 21. doi:10.3389/fonc.2021.618767 [8]Bates SE. Epigenetic Therapies for Cancer. N Engl J Med. 2020;383(7):650-663. doi:10.1056/NEJMra1805035 [9]Zewdie A, Kassie TD, Anagaw TF, et al. Advanced-stage breast cancer diagnosis and its determinants in Ethiopia: a systematic review and meta-analysis. BMC Womens Health. 2024;24(1):284. Published 2024 May 11. doi:10.1186/s12905-024-03133-9 [10]Garcia-Martinez L, Zhang Y, Nakata Y, Chan HL, Morey L. Epigenetic mechanisms in breast cancer therapy and resistance. Nat Commun. 2021;12(1):1786. Published 2021 Mar 19. doi:10.1038/s41467-021-22024-3 [11]Seo J, Min SK, Park HR, et al. Expression of Histone Deacetylases HDAC1, HDAC2, HDAC3, and HDAC6 in Invasive Ductal Carcinomas of the Breast. J Breast Cancer. 2014;17(4):323-331. doi:10.4048/jbc.2014.17.4.323. [12]Tang Z, Ding S, Huang H, et al. HDAC1 triggers the proliferation and migration of breast cancer cells via upregulation of interleukin-8. Biol Chem. 2017;398(12):1347-1356. doi:10.1515/hsz-2017-0155. [13]Pandey K, An HJ, Kim SK, et al. Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review. Int J Cancer. 2019;145(5):1179-1188. doi:10.1002/ijc.32020. [14]Cao L, Zhao S, Yang Q, et al. Chidamide Combined With Doxorubicin Induced p53-Driven Cell Cycle Arrest and Cell Apoptosis Reverse Multidrug Resistance of Breast Cancer. Front Oncol. 2021;11:614458. Published 2021 Mar 2. doi:10.3389/fonc.2021.614458 [15]Ito A, Kawaguchi Y, Lai CH, et al. MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. EMBO J. 2002;21(22):6236-6245. doi:10.1093/emboj/cdf616 [16]Chen SY, Zheng XW, Cai JX, et al. Histone deacetylase inhibitor reverses multidrug resistance by attenuating the nucleophosmin level through PI3K/Akt pathway in breast cancer. Int J Oncol. 2016;49(1):294-304. doi:10.3892/ijo.2016.3528 [17]Xu B, Zhang Q, Hu X, et al. Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. Acta Pharm Sin B. 2023;13(5):2250-2258. doi:10.1016/j.apsb.2023.02.001 [18]Jiang Z, Li W, Hu X, et al. Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer (ACE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(6):806-815. doi:10.1016/S1470-2045(19)30164-0 [19]Ryan QC, Headlee D, Acharya M, et al. Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J Clin Oncol. 2005;23(17):3912-3922. doi:10.1200/JCO.2005.02.188 [20]Kummar S, Gutierrez M, Gardner ER, et al. Phase I trial of MS-275, a histone deacetylase inhibitor, administered weekly in refractory solid tumors and lymphoid malignancies. Clin Cancer Res. 2007;13(18 Pt 1):5411-5417. doi:10.1158/1078-0432.CCR-07-0791 （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。

临床结果临床3期临床2期

2025-01-22

·米内网

【获批】石药拿下超10亿大品种

精彩内容近日，石药集团公告称，公司开发的瑞戈非尼片（40mg）获批生产并视同过评。这是一款小分子口服多靶点激酶抑制剂，2023年在中国三大终端六大市场（统计范围详见本文末）的销售额超过10亿元。2024年以来，石药集团已有12个品种获批生产并视同过评。瑞戈非尼是一款小分子口服多靶点激酶抑制剂，能阻断多种促进肿瘤生长的激酶，目前已获批的适应症包括转移性结直肠癌、局部晚期胃肠道间质瘤、肝细胞癌等。米内网数据显示，瑞戈非尼片2022年在中国三大终端六大市场的销售额突破10亿元，2023年以约10%的增速继续增长，2024上半年有所回落。近年来中国三大终端六大市场瑞戈非尼片销售情况（单位：万元）来源：米内网格局数据库在2023年蛋白激酶抑制剂TOP10产品中，瑞戈非尼片排位第十。甲磺酸奥希替尼片、盐酸安罗替尼胶囊、甲磺酸阿美替尼片依次位列前三，其中盐酸安罗替尼胶囊、甲磺酸阿美替尼片均为国产1类新药。 2023年中国三大终端六大市场蛋白激酶抑制剂TOP10产品注：标*为增速超10%来源：米内网格局数据库目前国内已有10家企业的瑞戈非尼片获批生产并视同过评，包括扬子江药业、南京正大天晴制药、豪森药业、齐鲁制药、湖南科伦制药、上海创诺制药、湖南明瑞制药、重庆药友制药、青峰医药、石药集团等；此外，北京双鹭药业、仁合熙德隆药业等企业的产品报产在审。 2024年以来，石药集团有恩朗苏拜单抗注射液（PD-1单抗）、普卢格列汀片（DPP-4抑制剂）2款1类新药首次获批上市；12个品种获批生产并视同过评，其中罗沙司他胶囊、哌柏西利片等为国内首仿+首家过评。 2024年以来石药集团获批上市的品种来源：米内网中国申报进度（MED）数据库注：米内网《中国三大终端六大市场药品竞争格局》，统计范围是：城市公立医院和县级公立医院、城市社区中心和乡镇卫生院、城市实体药店和网上药店，不含民营医院、私人诊所、村卫生室，不含县乡村药店；上述销售额以产品在终端的平均零售价计算。数据统计截至2025年1月21日，如有疏漏，欢迎指正。本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com 稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092 【分享、点赞、在看】点一点不失联哦

上市批准

2025-01-21

·Business Wire

NiKang Therapeutics® Announces First Patient Dosed in a Phase 1b/2 Study of NKT2152 in Combination with Standard-of-Care in First-Line Regimen for Hepatocellular Carcinoma

WILMINGTON, Del.--( BUSINESS WIRE )--NiKang Therapeutics ® Inc. (“NiKang”), a clinical-stage biotech company focused on developing innovative small molecule oncology medicines to bring transformative therapies to patients in need, today announced that the first patient has been dosed in the global randomized phase 1b/2 clinical study evaluating NKT2152, a highly potent, selective and orally bioavailable small molecule HIF2α inhibitor, in combination with standard-of-care regimen of atezolizumab (Tecentriq®) and bevacizumab (Avastin®) in the first-line treatment of patients with advanced or metastatic HCC. This study is being conducted under a clinical trial collaboration with F. Hoffmann-La Roche Ltd (“Roche”) as part of Roche’s MORPHEUS-liver platform trial (NCT04524871). “ The commencement of this randomized study of NKT2152 in partnership with Roche represents a significant milestone in the advancement of NKT2152 for the treatment of tumors beyond ccRCC,” said Zhenhai Gao, Ph.D., co-founder, president, and CEO of NiKang. “ NKT2152 has demonstrated significant anti-tumor efficacy and a favorable safety profile not only in human ccRCC patients but also in preclinical xenograft models of solid tumors beyond ccRCC, underscoring its potential for broad application in human cancer treatments. HCC is of particular interest due to the compelling scientific rationale supporting NKT2152 and robust preclinical data. With high potency, selectivity, and unique human pharmacokinetic (PK) profile characterized by higher systemic exposure, a larger volume of distribution, and a longer half-life, NKT2152 emerges as an ideal candidate for combination with antibody-based regimens to treat solid tumors beyond ccRCC, where higher drug exposure may be necessary. We are enthusiastic about further exploring NKT2152’s potential in the first-line treatment of HCC patients through this randomized trial”. About NKT2152 NKT2152 is a potent, selective and orally available small molecule HIF2α inhibitor which binds to HIF2α allosterically and disrupts the HIF2α/HIF1β transcription factor complex, thereby reducing the production of proteins which lead to tumorigenesis. NKT2152 is currently under evaluation in a Phase 1/2 clinical study in ccRCC as a single agent (NCT05119335) and a Phase 2 clinical study in ccRCC in combination with palbociclib and sasanlimab (NCT05935748). A third clinical study, as part of Roche’s MORPHEUS-liver platform trial, evaluating the combination with standard-of-care atezolizumab and bevacizumab in first-line unresectable/advance hepatocellular carcinoma (HCC) (NCT04524871) is ongoing. About NiKang Therapeutics NiKang Therapeutics is a clinical-stage biotech company focused on discovering and developing innovative small molecule oncology medicines to bring transformative therapies to patients in need. Our target selection is driven by deep insight into disease biology and molecular pathways. Our discovery approach is informed by target structure biology and capitalizes on structure-based drug design. The successful implementation of our strategy enables us to rapidly and efficiently discover and advance proprietary drug candidates with the most desirable pharmacological features into clinical studies. We have successfully advanced three programs into clinical trials, including NKT2152 (HIF2α), NKT3447 (CDK2), and NKT3964 (CDK2). For more information, please visit http://www.nikangtx.com Tecentriq® (atezolizumab) and Avastin® (bevacizumab) are registered trademarks of Genentech, a member of the Roche Group.

临床2期

100 项与哌柏西利相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10372	哌柏西利	L01XE33	DB09073

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
复发性乳腺癌	日本	Pfizer Japan, Inc.	2017-09-27
HR阳性/HER2阴性乳腺癌	美国	Pfizer Inc.	2016-02-19
ER阳性/HER2阴性乳腺癌	美国	Pfizer Inc.	2015-02-03

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
HPV相关鳞状细胞癌	临床3期	美国	Pfizer Inc.	2022-04-06
头颈部鳞状细胞癌	临床3期	美国	Pfizer Inc.	2022-04-06
转移性头颈部鳞状细胞癌	临床3期	美国	Pfizer Inc.	2022-04-06
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	奥地利	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	法国	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	匈牙利	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	意大利	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	西班牙	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	瑞士	Pfizer Inc.	2019-08-27
HER2 阴性乳腺癌	临床3期	日本	Pfizer Inc.	2019-07-16

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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


NCT04256941 (CTgov)	临床2期	转移性乳腺癌	4	Fulvestrant (Fulvestrant)	選觸鑰憲淵簾憲衊製淵(網製選遞襯淵窪衊願衊) = 鬱獵願顧壓窪範積膚觸遞憲醖觸觸艱製餘構選 (蓋鹽齋鬱鬱蓋壓簾範鹹, 窪鑰艱艱糧獵簾顧構衊 ~ 築鏇夢夢淵顧簾鏇選遞) 更多	-	2024-12-27
				palbociclib (Ibrance)+fulvestrant (Continuing AI After Randomization)	選觸鑰憲淵簾憲衊製淵(網製選遞襯淵窪衊願衊) = 構餘醖齋齋顧糧憲醖網遞憲醖觸觸艱製餘構選 (蓋鹽齋鬱鬱蓋壓簾範鹹, 積蓋糧獵齋鹽鑰蓋構鹹 ~ 鹹壓鏇選蓋醖積繭遞齋) 更多
NCT02297438 (PALOMA-4, Pubmed \| Chin Med J (Engl))	临床3期	ER阳性/HER2阴性乳腺癌一线 ER+ \| HER2−	-	Palbociclib plus Letrozole	構簾構鬱範積膚積鹽鏇(餘獵艱鹽鬱願獵製簾顧): mean change from baseline = 0.97 (95% CI, 0.05 ~ 1.89), P-Value = 0.038 更多	积极	2024-12-19
				Placebo plus Letrozole
NCT03644186 (TOUCH, CTgov)	临床2期	ER阳性/HER2阳性乳腺癌 \| HER2阳性乳腺癌 \| HR阳性/HER2阳性乳腺癌	147	Trastuzumab+Paclitaxel+pertuzumab (Paclitaxel Plus Trastuzumab and Pertuzumab)	糧築糧淵積獵鹹齋憲憲(廠築衊鹽膚膚範廠衊醖) = 衊顧網糧觸獵願範選壓鑰壓鏇餘蓋齋艱簾餘鹽 (鬱積襯範鹹構廠衊遞醖, 簾鹹窪積鑰廠觸繭夢鏇 ~ 膚願鹹艱觸遞膚遞鏇醖) 更多	-	2024-12-13
				Trastuzumab+Letrozole+palbociclib+pertuzumab (Palbociclib Plus Letrozole Plus Trastuzumab and Pertuzumab)	糧築糧淵積獵鹹齋憲憲(廠築衊鹽膚膚範廠衊醖) = 鬱膚齋淵顧襯製鑰範糧鑰壓鏇餘蓋齋艱簾餘鹽 (鬱積襯範鹹構廠衊遞醖, 簾鹹顧鹹齋鏇繭範夢鹽 ~ 齋鏇鹽觸築簾網衊鏇顧) 更多
NCT02947685 (PATINA, Company_Website) 人工标引	临床3期	HR阳性/HER2阳性乳腺癌一线 HER2 Positive \| Hormone Receptor Positive	518	IBRANCE + anti-HER2 therapy + endocrine therapy	夢糧淵膚壓顧醖壓壓壓(鬱淵鬱憲遞遞構糧觸願) = 構鑰襯醖襯選餘憲衊淵糧簾築衊網襯鬱顧鹹繭 (網襯糧襯鑰窪衊齋獵選, 32.4 ~ 60.9) 更多	积极	2024-12-12
				Anti-HER2 therapy + endocrine therapy	夢糧淵膚壓顧醖壓壓壓(鬱淵鬱憲遞遞構糧觸願) = 鬱淵餘顧衊選獵願襯憲糧簾築衊網襯鬱顧鹹繭 (網襯糧襯鑰窪衊齋獵選, 23.3 ~ 38.6) 更多
NCT06390839 (CTgov)	临床2期	难治恶性实体肿瘤 \| 晚期恶性实体瘤 \| 晚期淋巴瘤 ... 更多	43	Computed Tomography+palbociclib	築艱鹽鹹鹽願夢鹹餘構(築鑰膚襯選蓋簾衊鏇鬱) = 鏇醖齋鬱築繭顧壓糧襯醖簾網願鬱憲獵構積膚 (選範夢衊鏇築壓鬱範遞, 壓衊製製構膚餘範憲夢 ~ 糧膚範艱糧艱夢鹹蓋艱) 更多	-	2024-12-10
NCT02491983 (PARSIFAL, CTgov)	临床2期	转移性HER2阴性乳腺癌 \| ER阳性/HER2阴性乳腺癌 \| 转移性乳腺癌	486	Letrozole+palbociclib (Arm A)	製廠憲鹽齋鬱繭鹹壓衊(製膚蓋範築顧顧顧襯鹹) = 繭糧鑰鏇鹽願衊願積獵範醖觸鹽蓋鹹窪範齋觸 (齋壓構膚獵觸壓繭選鏇, 積鏇網衊顧憲鏇願壓膚 ~ 遞鹽遞構繭淵餘壓醖鹽) 更多	-	2024-12-09
				Fulvestrant+palbociclib (Arm B)	製廠憲鹽齋鬱繭鹹壓衊(製膚蓋範築顧顧顧襯鹹) = 醖夢願窪網膚鏇選醖構範醖觸鹽蓋鹹窪範齋觸 (齋壓構膚獵觸壓繭選鏇, 觸窪築壓繭襯醖鏇齋膚 ~ 醖膚網窪糧醖鑰製鏇壓) 更多
ESMO_ASIA2024 人工标引	N/A	HR阳性/HER2阴性乳腺癌一线 HER2 Negative \| Hormone Receptor Positive	377	Palbociclib	齋鏇獵願鹹憲鏇壓糧餘(襯獵鏇遞壓鏇醖壓獵鹹) = 鹽構壓鹹膚遞鹹獵壓網淵艱簾憲蓋觸餘鏇糧鹽 (鹹糧憲蓋襯製網簾艱鬱 ) 更多	相似	2024-12-07
				Ribociclib	齋鏇獵願鹹憲鏇壓糧餘(襯獵鏇遞壓鏇醖壓獵鹹) = 窪鹹願淵願憲醖膚築積淵艱簾憲蓋觸餘鏇糧鹽 (鹹糧憲蓋襯製網簾艱鬱 ) 更多
NCT05361655 (Pubmed \| Oncologist)	N/A	心血管疾病 \| 转移性乳腺癌一线 HR+ \| HER2−	469	Palbociclib plus aromatase inhibitor	膚壓鑰齋觸鹹窪顧願齋(艱選壓遞築鏇襯窪憲鑰) = 範餘齋衊醖獵廠鏇窪窪夢願鹽鏇積廠鏇選獵餘 (鬱鹹壓齋製鏇鏇鏇顧願 ) 更多	积极	2024-12-06
				Aromatase inhibitor alone	膚壓鑰齋觸鹹窪顧願齋(艱選壓遞築鏇襯窪憲鑰) = 糧積製膚襯憲糧獵顧膚夢願鹽鏇積廠鏇選獵餘 (鬱鹹壓齋製鏇鏇鏇顧願 ) 更多
EAY131 (Pubmed \| Clin Cancer Res)	临床2期	CDK4- \| CDK6 amplification	-	Palbociclib 125 mg	膚齋遞製壓夢選範範鹹(憲憲壓膚憲積窪積鹹夢) = 醖網製鹽選蓋蓋遞憲鏇繭鑰淵鹽艱齋憲鏇築鹽 (艱憲繭衊糧糧繭襯窪簾 ) 更多	不佳	2024-12-03
NCT04130152 (Pubmed \| NPJ Breast Cancer)	早期临床1期	HR阳性/HER2阴性乳腺癌	-	Palbociclib plus Letrozole	選製醖願鏇鏇鏇網鬱遞(艱蓋齋獵顧廠憲膚窪鬱) = 鹹範遞憲觸鹽遞鹹憲選網範製糧醖艱窪蓋鬱糧 (窪觸襯製築選膚糧衊遞 ) 更多	-	2024-11-26