Delving into the Latest Updates on Unecritinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

安奈克替尼

+ [1]

Target

ALK x ROS1 x c-Met

Mechanism

ALK inhibitors(Anaplastic lymphoma kinase inhibitors), ROS1 inhibitors(Proto-oncogene tyrosine-protein kinase ROS inhibitors), c-Met inhibitors(Hepatocyte growth factor receptor inhibitors)

Therapeutic Areas

NeoplasmsRespiratory DiseasesImmune System Diseases+ [2]

Active Indication

Reactive oxygen species 1 positive non-small cell lung cancerAnaplastic Large-Cell Lymphoma

Inactive Indication

Advanced cancerAdvanced Malignant Solid NeoplasmLocally Advanced Malignant Neoplasm+ [1]

Originator Organization

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Active Organization

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Southeast University

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (24 Apr 2024),

Reactive oxygen species 1 positive non-small cell lung cancer

RegulationSpecial Review Project (CN)

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Structure/Sequence

Molecular FormulaC23H24Cl2FN5O2

InChIKeyHBWSXXBJOQKNBL-CYBMUJFWSA-N

CAS Registry1418026-92-2

Primary purpose To evaluate the effectiveness of TQ-B3101 capsules in treating subjects with advanced malignant tumors; Secondary purpose To evaluate the safety of TQ-B3101 capsules in treating subjects with advanced malignant tumors; To explore the relationship between genetic abnormalities such as ALK, MET, ROS1, NTRK, AXL and the efficacy of TQ-B3101 capsules;

Start Date28 Sep 2021

Sponsor / Collaborator

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

[+1]

NCT04804904

/ CompletedPhase 1

A Single Center, Phase I, Open-Label, Randomized, Crossover Study to Evaluate the Effect of Food on the Pharmacokinetics of TQB3101 in Healthy Subjects

Evaluate the effect of food on the pharmacokinetics of TQB3101 in healthy subjects.

Start Date20 May 2021

Sponsor / Collaborator

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

CTR20202392

/ CompletedPhase 1

评估食物对TQ-B3101胶囊在健康成年受试者中药代动力学影响的随机、开放、单中心、两周期、两交叉I期临床试验

[Translation] A randomized, open-label, single-center, two-period, two-crossover phase I clinical trial to evaluate the effect of food on the pharmacokinetics of TQ-B3101 capsules in healthy adult subjects

评价食物对中国健康成年受试者口服TQ-B3101胶囊后药代动力学的影响，观察健康受试者单剂量口服TQ-B3101胶囊的安全性。

[Translation]

To evaluate the effect of food on the pharmacokinetics of TQ-B3101 capsules after oral administration to healthy Chinese adult subjects and to observe the safety of a single oral dose of TQ-B3101 capsules in healthy subjects.

Start Date17 May 2021

Sponsor / Collaborator

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

[+1]

100 Clinical Results associated with Unecritinib

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100 Translational Medicine associated with Unecritinib

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100 Patents (Medical) associated with Unecritinib

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3

Literatures (Medical) associated with Unecritinib

01 Aug 2024·Journal of Pharmaceutical and Biomedical Analysis

Simultaneous determination of unecritinib (TQ-B3101) and its active metabolite crizotinib in rat plasma by LC-MS/MS：An application to pharmacokinetic studies

Article

Author: Chen, Xiaoyan ; Cui, Xinran ; Wang, Hong ; Zhang, Yuchen ; Chen, Huixian ; Zhou, Jialan

Unecritinib (TQ-B3101) is a selective tyrosine kinase receptor inhibitor. In the study, in vitro metabolic experiments revealed that the hydrolysis of TQ-B3101 was mainly catalyzed by carboxylesterase 2 (CES2), followed by CES1. Next, a sensitive and reliable LC-MS/MS method was established for the simultaneous determination of TQ-B3101 and its metabolite crizotinib in rat plasma. To prevent in vitro hydrolysis of TQ-B3101, sodium fluoride, the CESs inhibitor at a concentration of 2 M, was immediately added after whole blood collection. Plasma samples were extracted by acetonitrile-induced protein precipitation method, and chromatographically separated on a Gemini C₁₈ column (50 mm × 2.0 mm i.d., 5 μm) using gradient elution with a mobile phase of 0.1% formic acid and 5 mmol/L ammonium acetate with 0.1% formic acid. The retention times for TQ-B3101 and crizotinib were 2.61 and 2.38 min, respectively. The analytes were detected with tandem mass spectrometer by positive electrospray ionization, using the ion transitions at m/z 492.3 → 302.3 for TQ-B3101, m/z 450.3 → 260.3 for crizotinib, and m/z 494.0 → 394.3 for imatinib (internal standard). Method validation was conducted in the linear range of 1.00-800 ng/mL for the two analytes. The precision, accuracy and stabilities all met the acceptance criteria. The pharmacokinetic study indicated that TQ-B3101 was rapidly hydrolyzed to crizotinib with the elimination half-life of 1.11 h after a single gavage administration of 27 mg/kg to Sprague-Dawley rats, and the plasma exposure of TQ-B3101 was only 2.98% of that of crizotinib.

30 Jun 2023·Signal transduction and targeted therapy

Efficacy, safety and pharmacokinetics of Unecritinib (TQ-B3101) for patients with ROS1 positive advanced non-small cell lung cancer: a Phase I/II Trial.

Article

Author: Pan, Hongming ; Yang, Zhixiong ; Yao, Yu ; Zhuang, Wu ; Yu, Zhuang ; Zhong, Diansheng ; Fang, Yong ; Li, Kai ; Cao, Lejie ; Li, Weidong ; Lu, Shun ; Cang, Shundong ; Ma, Zhiyong ; Cui, Jiuwei ; Shi, Jianhua ; Zhang, Jie ; Min, Xuhong ; Xu, Xingxiang ; Zhou, Zhen ; Zhang, Yang ; Fang, Jian ; Wang, Yan ; Wang, Tao ; Wang, Xiuwen ; He, Jianxing ; Shu, Yongqian ; Cai, Xiuyu ; Wu, Lin ; Yu, Yan ; Yang, Huaping ; Li, Man ; Zhu, Jiajia ; Wang, Xicheng ; Wen, Xinxuan

This phase I/II trial characterized the tolerability, safety, and antitumor activities of unecritinib, a novel derivative of crizotinib and a multi-tyrosine kinase inhibitor targeting ROS1, ALK, and c-MET, in advanced tumors and ROS1 inhibitor-naive advanced or metastatic non-small cell lung cancer (NSCLC) harboring ROS1 rearrangements. Eligible patients received unecritinib 100, 200, and 300 mg QD, and 200, 250, 300, and 350 mg BID in a 3 + 3 design during dose escalation and 300 and 350 mg BID during expansion. Phase II trial patients received unecritinib 300 mg BID in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) per independent review committee (IRC). Key secondary endpoints included intracranial ORR and safety. The ORR of 36 efficacy evaluable patients in the phase I trial was 63.9% (95% CI 46.2%, 79.2%). In the phase II trial, 111 eligible patients in the main study cohort received unecritinib. The ORR per IRC was 80.2% (95% CI 71.5%, 87.1%) and the median progression-free survival (PFS) per IRC was 16.5 months (95% CI 10.2, 27.0). Additionally, 46.9% of the patients who received recommended phase II dose of 300 mg BID experienced grade 3 or higher treatment-related adverse events. Treatment-related ocular disorders and neurotoxicity occurred in 28.1% and 34.4% of patients, respectively, but none was grade 3 or higher. Unecritinib is efficacious and safe for ROS1 inhibitor-naive patients with ROS1-positive advanced NSCLC, particularly patients with brain metastases at baseline, strongly supporting that unecritinib should become one of the standards of care for ROS1-positive NSCLC.ClinicalTrials.gov identifier: NCT03019276 and NCT03972189.

Frontiers in PharmacologyQ2 · MEDICINE

Population Pharmacokinetic Modeling and Simulation of TQ-B3101 to Inform Dosing in Pediatric Patients With Solid Tumors

Q2 · MEDICINE

ArticleOA

Author: Xie, Simin ; Wu, Huali ; Pan, Hong ; Lu, Ye ; Yang, Fen ; Li, Su ; Liao, Harry ; Wang, Bing ; Bo, Yunhai ; Lu, Qin

Background: TQ-B3101 is a novel kinase inhibitor currently in development for the treatment of advanced malignant solid tumor and relapsed or refractory ALK-positive anaplastic large cell lymphoma.Methods: A population pharmacokinetic model was developed using data collected from a Phase 1 study and a Phase 2 study to characterize the pharmacokinetic of TQ-B3101 and its active metabolite (TQ-B3101M). The final model was used to optimize dosing of TQ-B3101 for pediatric patients (6-<18 years) with anaplastic large cell lymphoma.Results: The pharmacokinetic of TQ-B3101 and TQ-B3101M was adequately described by a 1-compartment model with first-order absorption and elimination for parent drug coupled with a 2-compartment model with time-dependent clearance for the metabolite. The clearance of TQ-B3101M decreased over time with a maximum fractional reduction of 0.41. The estimated apparent clearance and apparent volume of distribution of TQ-B3101 were 2850 L/h and 4200 L, respectively. The elimination half-life of TQ-B3101 was 1.0 h. The distribution and elimination half-lives of TQ-B3101M at steady state were 4.9 and 39.4 h, respectively. The projected exposure of TQ-B3101M in virtual pediatric population following the body surface area tiered dosing regimen was similar to that in children pediatric patients after the recommended pediatric dose of crizotinib (280 mg/m2 twice daily), an analog of TQ-B3101M.Conclusion: A population pharmacokinetic model was developed to provide optimal dose of regimen for further development of TQ-B3101 in pediatric patients with anaplastic large cell lymphoma.

100 Deals associated with Unecritinib

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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Reactive oxygen species 1 positive non-small cell lung cancer	CN	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	24 Apr 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Locally Advanced Malignant Neoplasm	Preclinical	CN	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	05 Aug 2020
Non-Small Cell Lung Cancer	Discovery	CN	Southeast University	26 Jun 2023
Advanced Malignant Solid Neoplasm	Discovery	CN	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	28 Sep 2021
Advanced Malignant Solid Neoplasm	Discovery	CN	Southeast University	28 Sep 2021
Advanced cancer	Discovery	CN	Southeast University	17 Jul 2020
Anaplastic Large-Cell Lymphoma	Discovery	CN	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	29 Nov 2019
Recurrent Anaplastic Large Cell Lymphoma	Discovery	CN	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	29 Nov 2019
Reactive oxygen species 1 positive non-small cell lung cancer	Discovery	CN	Southeast University	17 Jul 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03972189 (TQ-B3101-II-01, WCLC2024) Manual	Phase 2	Reactive oxygen species 1 positive non-small cell lung cancer	111	Unecritinib 300 mg BID	(iquoielokz) = mqfdgdmrpf icgtwhlcgx (evqlwycxgn, 72.55 - 87.89) View more	Positive	10 Sep 2024
NCT03972189 (TQ-B3101-II-01, WCLC2024) Manual	Phase 2		111	Unecritinib (baseline brain metastases)	(iquoielokz) = ejdnzjpkpb icgtwhlcgx (evqlwycxgn, 54.48 - 86.70) View more	Positive	10 Sep 2024
NCT03019276 (Pubmed) Manual	Phase 1	Reactive oxygen species 1 positive non-small cell lung cancer ROS1 Positive	36	Unecritinib	(yhmwhxxwwy) = vvorbpuwog lugzvlcetw (xhwfmgtpvv, 46.2 - 79.2)	Positive	30 Jun 2023
NCT03972189 (Pubmed) Manual	Phase 2	Reactive oxygen species 1 positive non-small cell lung cancer ROS1 Positive	111	unecritinib 300 mg	(gkemocgmsz) = goqyhphryk nivzxuppgk (wioplzhtcw, 71.5 - 87.1) View more	Positive	30 Jun 2023
NCT04306887 (TQ-B3101-II-02, ASH2022) Manual	Phase 1	ALK-positive anaplastic large cell lymphoma ALK Positive	7	TQ-B3101	(ahqxvxisgn) = eosiqqvmjv cvjzbvznlc (aiwitazdfu ) View more	Positive	11 Dec 2022
NCT03972189 (ESMO_ELCC2022) Manual	Phase 2	Reactive oxygen species 1 positive non-small cell lung cancer First line ROS1-positive	111	TQ-B3101 300 mg	(htknmwcbkr) = vunudrwmfj wuukyglztw (fvxbwldggm, 69.6 - 85.6) View more	Positive	30 Mar 2022
NCT03019276 (ASCO 12020 \| ASCO 22020) Manual	Phase 1	Advanced cancer ALK Positive \| ROS1 Positive \| MET Amplification	30	TQ-B3101 300mg BID	(emzgbhhdwf) = hyodktyrxe myajvyodxl (phxiznmhcs )	Positive	29 May 2020
NCT03019276 (ASCO 12020 \| ASCO 22020) Manual	Phase 1		30	TQ-B3101 350mg BID	(izuriyuwsc) = sdaoyqunbz zwxfejvcnd (qvcbsrdcli ) View more	Positive	29 May 2020