Delving into the Latest Updates on Docetaxel polymeric micelle with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Docetaxel-PM, NanoxelM, 多西他赛-PM

+ [4]

Target

Tubulin

Mechanism

Tubulin modulators, Mitosis inhibitors, Tubulin polymerisation promoters

Therapeutic Areas

NeoplasmsUrogenital DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication

Bladder CancerHead and Neck NeoplasmsAdvanced Malignant Solid Neoplasm+ [2]

Inactive Indication

Non-Muscle Invasive Bladder NeoplasmsSquamous cell carcinoma of head and neck metastatic

Originator Organization

Samyang Biopharmaceuticals Corp.

Active Organization

Shandong Hubble Kisen Biological Technology Co Ltd

Shanxi Kangbao Biological Product Co. Ltd.Samyang Biopharmaceuticals Corp.

+ [1]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

KR (01 Jul 2016),

Bladder CancerHead and Neck Neoplasms

Regulation-

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Structure

Molecular FormulaC43H53NO14

InChIKeyZDZOTLJHXYCWBA-VCVYQWHSSA-N

CAS Registry114977-28-5

剂量递增研究（Ⅰa期）主要目的：评估注射用多西他赛聚合物胶束在晚期实体瘤患者中的安全性和耐受性；确定最大耐受剂量（MTD）和/或推荐剂量（RD）。次要目的：评估注射用多西他赛聚合物胶束在晚期实体瘤患者中的药代动力学（PK）特征；评估注射用多西他赛聚合物胶束在晚期实体瘤患者中的初步疗效。

[Translation]

Dose escalation study (Phase Ia) Primary objectives: To evaluate the safety and tolerability of docetaxel polymer micelles for injection in patients with advanced solid tumors; to determine the maximum tolerated dose (MTD) and/or recommended dose (RD). Secondary objectives: To evaluate the pharmacokinetic (PK) characteristics of docetaxel polymer micelles for injection in patients with advanced solid tumors; to evaluate the preliminary efficacy of docetaxel polymer micelles for injection in patients with advanced solid tumors.

Start Date14 Jun 2023

Sponsor / Collaborator

Shanxi Kangbao Biological Product Co. Ltd.

NCT05207514 / TerminatedPhase 3

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

Start Date31 Mar 2022

Sponsor / Collaborator

Samyang Biopharmaceuticals Corp.

CTR20213207 / RecruitingPhase 2

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

[Translation] An open-label, multi-cohort phase II clinical study to evaluate the efficacy and safety of docetaxel polymer micelles for injection in patients with advanced malignant solid tumors

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；

[Translation]

1. Dose confirmation phase: evaluate the safety and tolerability of three dosing regimens of HT001 in patients with advanced esophageal cancer and determine the subsequent recommended dosing regimen; 2. Cohort expansion phase: evaluate the efficacy of HT001 in patients with advanced solid tumors;

Start Date11 Mar 2022

Sponsor / Collaborator

Suzhou Hightechbio Biotechnology Co. Ltd.

100 Clinical Results associated with Docetaxel polymeric micelle

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100 Translational Medicine associated with Docetaxel polymeric micelle

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100 Patents (Medical) associated with Docetaxel polymeric micelle

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7

Literatures (Medical) associated with Docetaxel polymeric micelle

01 Oct 2023·Cancer

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

Article

Author: Lee, Jiyun ; Lee, Keun-Wook ; Choi, Yoon Ji ; Park, Sehhoon ; Shin, Seong Hoon ; 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.

11 May 2022·ACS Applied Materials & InterfacesQ2 · MATERIALS SCIENCE

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

Q2 · MATERIALS SCIENCE

Article

Author: Chen, Zhongping ; Cai, Xiaohui ; Lu, Min ; Huang, Xu ; Weng, Lingyan ; Zhu, Li ; Luo, Qianqian ; 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.

01 Mar 2019·Journal of Controlled ReleaseQ1 · MEDICINE

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

Q1 · MEDICINE

Article

Author: 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.

100 Deals associated with Docetaxel polymeric micelle

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	L01CD02	DB01248

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Bladder Cancer	KR	Samyang Biopharmaceuticals Corp.	01 Jul 2016
Head and Neck Neoplasms	KR	Samyang Biopharmaceuticals Corp.	01 Jul 2016

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	CN	Shanxi Kangbao Biological Product Co. Ltd.	14 Jun 2023
HER2-negative breast cancer	Phase 1	CN	Shandong Hubble Kisen Biological Technology Co Ltd	13 May 2019
Squamous cell carcinoma of head and neck metastatic	Phase 1	KR	Samyang Biopharmaceuticals Corp.	01 Oct 2015
Malignant ascites	IND Approval	CN	Nanjing Simcere Dongyuan Pharmaceutical Co. Ltd.	31 May 2022
Breast Cancer	Discovery	KR	Samyang Biopharmaceuticals Corp.	31 Mar 2022
Non-Muscle Invasive Bladder Neoplasms	Discovery	KR	Samyang Biopharmaceuticals Corp.	01 Jan 2017