Open-label, Randomized, Active-controlled, Multicenter, Phase III Clinical Trial to Compare the Efficacy and the Safety of Taxotere and Nanoxel M as Neoadjuvant Chemotherapy in Breast Cancer

Phase III Clinical Trial to Compare the Efficacy and the Safety of AC(Doxorubicin, Cyclophosphamide) Followed by 4 Cycles Taxotere Versus AC(Doxorubicin, Cyclophosphamide) Followed by 4 Cycles Nanoxel M as Neoadjuvant Chemotherapy in Patients With Breast Cancer

开始日期2022-03-31

申办/合作机构

Samyang Biopharmaceuticals Corp.

CTR20213207 / Recruiting临床2期

评估注射用多西他赛聚合物胶束在晚期恶性实体瘤患者中有效性和安全性的开放性、多队列II期临床研究

1. 剂量确认阶段：评估HT001三种给药方案在晚期食管癌患者中的安全性及耐受性，确定后续推荐给药方案； 2. 队列拓展阶段：评估HT001在晚期实体瘤患者中的疗效；

开始日期2022-03-11

申办/合作机构

苏州海特比奥生物技术有限公司

100 项与多西他赛聚合物胶束相关的临床结果

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100 项与多西他赛聚合物胶束相关的转化医学

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100 项与多西他赛聚合物胶束相关的专利（医药）

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项与多西他赛聚合物胶束相关的文献（医药）

2023-10-01·Cancer

A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.

Article

作者: Lee, Jiyun ; Lee, Keun-Wook ; Choi, Yoon Ji ; Shin, Seong Hoon ; Park, Sehhoon ; Oh, So Yeon ; Kim, Ji-Won ; An, Ho-Jung ; Kim, Jae-Joon ; Lee, Se-Hoon ; Kim, Ju Won ; Shim, Byoung-Yong ; Park, Lee Chun ; Seo, Seyoung ; Kang, Eun Joo ; Kim, Sung-Bae ; Kim, Min Kyoung ; Ahn, Myung-Ju ; Jung, Hyun Ae

BACKGROUNDSalivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab.METHODSThis was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m² ) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR).RESULTSA total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively.CONCLUSIONSThe combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC.PLAIN LANGUAGE SUMMARYSalivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.

2022-05-11·ACS Applied Materials & Interfaces2区 · 材料科学

Hypoxia-Responsive Stereocomplex Polymeric Micelles with Improved Drug Loading Inhibit Breast Cancer Metastasis in an Orthotopic Murine Model

2区 · 材料科学

Article

作者: Chen, Zhongping ; Cai, Xiaohui ; Lu, Min ; Huang, Xu ; Weng, Lingyan ; Luo, Qianqian ; Zhu, Li ; Liu, Xuemeng ; Sun, Jiajia

Tumor metastasis is a leading cause of breast cancer-related death. Taxane-loaded polymeric formulations, such as Genexol PM and Nanoxel M using poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) micelles as drug carriers, have been approved for the treatment of metastatic breast cancer. Unfortunately, the physical instability of PEG-PLA micelles, leading to poor drug loading, premature drug leakage, and consequently limited drug delivery to tumors, largely hinders their therapeutic outcome. Inspired by the enantiomeric nature of PLA, this work developed stereocomplex PEG-PLA micelles through stereoselective interactions of enantiomeric PLA, which are further incorporated with a hypoxia-responsive moiety used as a hypoxia-cleavable linker of PEG and PLA, to maximize therapeutic outcomes. The results showed that the obtained micelles had high structural stability, showing improved drug loading for effective drug delivery to tumors as well as other tissues. Especially, they were capable of sensitively responding to the hypoxic tumor environment for drug release, reversing hypoxia-induced drug resistance and hypoxia-promoted cell migration for enhanced bioavailability under hypoxia. In vivo results further showed that the micelles, especially at a high dose, inhibited the growth of the primary tumor and improved tumor pathological conditions, consequently remarkably inhibiting its metastasis to the lungs and liver, while not causing any systemic toxicity. Hypoxia-responsive stereocomplex micelles thus emerge as a reliable drug delivery system to treat breast cancer metastasis.

2019-03-01·Journal of Controlled Release1区 · 医学

Poly(ethylene glycol)-block-poly(d,l-lactic acid) micelles containing oligo(lactic acid)8-paclitaxel prodrug: In Vivo conversion and antitumor efficacy

1区 · 医学

Article

作者: Shin, Dae Hwan ; Kwon, Glen S ; Chen, Karen E ; Tam, Yu Tong

Poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-b-PLA) micelles affect drug solubilization, and a paclitaxel (PTX) loaded-PEG-b-PLA micelle (PTX-PM) is approved for cancer treatment due to injection safety and dose escalation (Genexol-PM®) compared to Taxol®. However, PTX-PM is unstable in blood, has rapid clearance, and causes dose-limiting toxicity. We have synthesized a prodrug for PTX (7-OH), using oligo(lactic acid) as a novel pro-moiety (o(LA)₈-PTX) specifically for PEG-b-PLA micelles, gaining higher loading and slower release of o(LA)₈-PTX over PTX. Notably, o(LA)₈-PTX prodrug converts into PTX by a backbiting reaction in vitro, without requiring esterases. We hypothesize that o(LA)₈-PTX-loaded PEG-b-PLA micelles (o(LA)₈-PTX-PM) has a lower C_max and higher plasma AUC than PTX-PM for improved therapeutic effectiveness. In Sprague-Dawley rats at 10 mg/kg, compared to o(LA)₈-PTX-PM (10% w/w loading) and PTX-PM (10%), o(LA)₈-PTX-PM (50% w/w loading) produces a 2- and 3-fold higher plasma AUC_0-24 of PTX, lactic acid-PTX, and o(LA)₂-PTX (o(LA)_0-2-PTX), respectively. For o(LA)₈-PTX-PM at 10 and 50% w/w loading, PTX and lactic acid-PTX are major bioactive metabolites, respectively. Fast prodrug conversion of o(LA)₈-PTX in vivo versus in vitro (by backbiting) suggests that o(LA)₈ is a good substrate for esterases. At 60 mg/kg (qwx3), o(LA)₈-PTX-PM (50%) has higher antitumor activity than o(LA)₈-PTX-PM (10%) and PTX-PM (10%) in a syngeneic 4T1-luc breast tumor model based on measurements of tumor volume, 4T1-luc breast tumor bioluminescence, and survival. Importantly, intravenous administration of o(LA)₈-PTX-PM is well tolerated by BALB/c mice. In summary, oligo(lactic acid)₈-PTX is more compatible than PTX with PEG-b-PLA micelles, more stable, and may expand the role of PEG-b-PLA micelles from "solubilizer" into "nanocarrier" for PTX as a next-generation taxane for cancer.

项与多西他赛聚合物胶束相关的新闻（医药）

2024-03-19

·CPHI制药在线

先声药业第四款肿瘤药呼之欲出，苏维西塔单抗申请上市

关注并星标CPHI制药在线近日，先声药业发布公告宣布其注射用苏维西塔单抗的上市申请获NMPA受理，适应症为：联合化疗用于治疗含铂化疗治疗失败的复发性卵巢癌、输卵管癌或原发性腹膜癌。苏维西塔单抗由先声药业与Apexigen公司合作开发，是一款新一代重组人源化抗VEGF兔源单克隆抗体。临床前研究显示：同剂量下苏维西塔单抗在多个肿瘤模型中表现出比贝伐珠单抗更优抑瘤效果和相似毒性。 2024年1月，先声药业宣布苏维西塔单抗联合化疗用于含铂化疗方案治疗失败的复发性上皮卵巢癌、输卵管癌和原发性腹膜癌患者的3期临床试验SCORES达到主要研究终点--对比安慰剂联合化疗组，苏维西塔单抗组PFS显示出具有统计学意义和临床意义的改善，且在所有亚组均显示出PFS临床获益的一致性。此外，关键次要终点OS的数据尚未成熟，但苏维西塔单抗组显示出获益的趋势。安全性方面，苏维西塔单抗安全性可控，未出现新的安全性信号。卵巢癌是妇科肿瘤中病死率最高的恶性肿瘤，据悉2020年中国卵巢癌新发病例高达5.53万例，死亡病例达3.75万例。因起病隐匿，以及缺乏早期筛查手段，约70%的卵巢癌患者发现时已处于晚期。手术联合含铂化疗加减靶向维持治疗（如PARPi±贝伐珠单抗）是目前卵巢癌的主要治疗方式，但大多数患者会复发并最终进展为铂类耐药。铂耐药复发的卵巢癌患者预后差，且治疗选择有限。贝伐珠单抗也是一款抗VEGF单抗，但AURELIA研究结果显示：贝伐珠单抗联合化疗可延长铂耐药复发卵巢癌患者的无进展生存（PFS）（化疗+贝伐珠单抗组6.7个月vs.化疗组3.4个月），但不能延长总生存期（OS）。而且，安全性分析发现贝伐珠单抗可导致高血压、蛋白尿及消化道穿孔的发生率增加。与贝伐珠单抗相比，苏维西塔单抗联合化疗不仅可以延长铂耐药复发卵巢癌的PFS，还可以延长OS。苏维西塔单抗有望成为我国第一个适用于铂耐药卵巢癌患者的抗VEGF单抗。证券公司预测，若顺利获批，苏维西塔单抗2030年有望实现14.2亿销售额。先声药业肿瘤研发管线分析先声药业作为传统综合性制药龙头企业，现专注于向创新研发转型，研发管线主要涉及肿瘤、中枢神经系统和自身免疫三大领域。在肿瘤领域，先声药业已有三款产品获批上市，如曲拉西利、恩沃利单抗和恩度®️（重组人血管内皮抑制素注射液）。曲拉西利是先声药业从G1 Therapeutics公司引进的细胞周期蛋白依赖性激酶4和6(CDK4/6)抑制剂，2022年7月在国内被NMPA批准用于既往未接受过系统性化疗的广泛期小细胞肺癌（ES-SCLC）患者，在接受含铂类药物联合依托泊苷方案治疗前给药，以降低化疗引起的骨髓抑制的发生率。而且，曲拉西利还于2023年9月在国内申报新适应症，用于ES-SCLC患者在接受含拓扑替康方案治疗前给药，以降低化疗引起的骨髓抑制的发生率。恩沃利单抗是先声药业于2020年引进的一款皮下注射用PD-L1 抗体，先声药业拥有其在中国大陆的独家商业推广权。目前，该药已于2021年11月被NMPA批准用于治疗不可切除或转移性微卫星高度不稳定(MSI-H)或错配修复基因缺陷型(dMMR)的成人晚期实体瘤。恩度是国内第一个获批的抗血管生成靶向药，也是国内外唯一获准销售的内皮抑制素，2005年9月被批准联合NP化疗方案用于治疗初治或复治的Ⅲ/Ⅳ期非小细胞肺癌患者。此外，先声药业肿瘤研发管线还有多款新药，详见下表。整体来看，先声药业在研肿瘤药物大多处于临床前和1期临床。而且，这些药物除了从外部企业引进，还有多款是先声药业自主研发。其中多西他赛聚合物胶束是先声药业于2020年9月从苏州海特比奥生物技术有限公司引进。该药以两亲性生物相容性可降解材料聚乙二醇单甲醚聚乳酸嵌段聚合物（mPEG-PDLLA）作为增溶载体，大大提高了稳定性，并降低了配制要求，更方便临床使用。已完成的1期临床试验结果显示：多西他赛胶束在25mg/m2~100mg/m2范围内，患者均可耐受， 75mg/m2剂量组7例疗效可评估，其中2例部分缓解，2例疾病稳定，100mg/m2剂量组5例疗效可评估，均为疾病稳定。 SIM0395（paxalisib）是先声药业从Kazia Therapeutics Limited引进的一款可透过血脑屏障的PI3K/mTOR通路抑制剂，拟用于治疗胶质母细胞瘤（GBM）。已公布的2期临床试验的中期数据显示，paxalisib可延长MGMT非甲基化的新发GBM患者的PFS和OS。2021年12月，该药在国内获批临床。 SIM0270是先声药业旗下子公司先声再明原研的一款新型可透脑选择性雌激素受体降解剂（SERD），在首次人体1期临床中对经多线治疗失败的晚期或转移性ER+/HER2-乳腺癌患者展现出良好的耐受性和抗肿瘤活性。在第46届圣安东尼奥乳腺癌研讨会上公布的SIM0270单药和/或与哌柏西利或依维莫司联合治疗HR+/HER2-晚期或转移性乳腺癌的1a期临床试验数据显示：在50名疗效可评估患者中，在不同剂量上观察到4例确认的PR，其中3例伴有ESR1突变，客观缓解率（ORR）为8%。在40例临床获益率（CBR）疗效可评估人群中，CBR率为25%。而且，SIM0270安全性良好，大多数治疗期不良事件（TEAEs）为1-2级。 SIM0235是一种针对TNFR2的人源化IgG1单克隆抗体，可阻断内源性肿瘤坏死因子 (TNF) 对 TNFR2 的活化，从而降低TNFR2引发的免疫抑制和肿瘤增生，增强抗肿瘤免疫应答。此外，该药还能通过抗体依赖性细胞毒性 (ADCC) 和抗体依赖性细胞吞噬作用 (ADCP)，杀伤表达TNFR2的免疫抑制细胞，包括调节型T细胞和髓系来源的免疫抑制细胞。2023年3月，先声药业与默沙东达成临床开发合作，探索SIM0235联合PD-1抗体KEYTRUDA®️治疗晚期实体瘤及皮肤T细胞淋巴瘤（CTCL）的潜力。在临床前研究中，已观察到SIM0235与KEYTRUDA联用具有良好的作用，有望为肿瘤患者带来临床获益。 SIM0272是一款合成致死药物，作用于蛋白质精氨酸甲基转移酶5（PRMT5）。药代动力学研究显示，SIM0272倾向于分布在肿瘤内，肿瘤内药物浓度与血浆药物浓度比值是其他在研PRMT5抑制剂的10倍左右。而且，SIM0272在体外展现出对多种血液瘤和实体瘤细胞的增殖抑制活性，且单药能显著抑制多个小鼠CDX模型中的肿瘤生长。2022年3月，该药在国内获批临床，拟用于治疗晚期恶性肿瘤。 SIM0237是先声再明蛋白质工程技术平台自主开发的一种抗PD-L1单抗与减活IL-15/IL-15Rα sushi融合蛋白，可通过结合PD-L1，阻断PD-1/PD-L1免疫抑制通路，同时通过IL-15激活免疫系统，从而实现解除免疫抑制和激活免疫系统的双重协同效应，发挥抗肿瘤作用。临床前研究显示，SIM0237在小鼠肿瘤模型中药效优于PD-L1单药和IL-15单药，有较高的临床开发潜力。 SIM0348是一种基于IgG1的人源化TIGIT/PVRIG双特异性抗体。临床前数据显示，SIM0348能有效促进NK细胞对人结直肠癌细胞和人血液白血病细胞的杀伤，同时还能显著增强抗原特异性CD8+T细胞分泌IFN-γ因子，效果优于PVRIG单抗和TIGIT单抗联用，且与抗PD-L1抗体联合显示出了显著的联用效果，优于任一单药药效且优于三药联用。2023年3月，该药治疗晚期实体瘤的1期临床试验完成首例患者给药。总结肿瘤是全球最大药物市场，每个药企都期望从中分一杯羹，先声药业也不例外，在肿瘤领域布局广泛。目前，先声药业已有三款肿瘤药物获批上市，第四款肿瘤药物已申请上市，多款新靶点药物进入临床。期待先声药业肿瘤管线早日开花结果。【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期申请上市上市批准临床结果

100 项与多西他赛聚合物胶束相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	L01CD02	DB01248

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
膀胱癌	韩国	Samyang Biopharmaceuticals Corp.	2016-07-01
头颈部肿瘤	韩国	Samyang Biopharmaceuticals Corp.	2016-07-01

未上市

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
晚期恶性实体瘤	临床1期	中国	山西康宝生物制品股份有限公司	2023-06-14
乳腺癌	临床1期	韩国	Samyang Biopharmaceuticals Corp.	2022-03-31
HER2 阴性乳腺癌	临床1期	中国	山东华铂凯盛生物科技有限公司	2019-05-13
非肌层浸润性膀胱肿瘤	临床1期	韩国	Samyang Biopharmaceuticals Corp.	2017-01-01
转移性头颈部鳞状细胞癌	临床1期	韩国	Samyang Biopharmaceuticals Corp.	2015-10-01
恶性腹水	临床申请批准	中国	先声药业有限公司	2022-05-31