Delving into the Latest Updates on Glumetinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

6-(1-methyl-1h-pyrazol-4-yl)-1-((6-(1-methyl-1h-pyrazol-4-yl)imidazo(1,2-a)pyridin-3-yl)sulfonyl)-1h-pyrazolo(4,3-b)pyridine, Gumarontinib, Gumarontinib Hydrate

+ [5]

Target

c-Met

Mechanism

c-Met inhibitors(Hepatocyte growth factor receptor inhibitors)

Therapeutic Areas

NeoplasmsRespiratory DiseasesDigestive System Disorders+ [1]

Active Indication

c-Met positive non-small cell lung cancerMET Exon 14 Skipping Mutation Non-small Cell Lung Cancermetastatic non-small cell lung cancer+ [4]

Inactive Indication

Recurrent Non-Small Cell Lung Cancer

Originator Organization

Shanghai Institute of Materia Medica Chinese Academy of Sci

Haihe Biopharma Co., Ltd.

Active Organization

Shanghai Green Valley Pharmaceutical Co., Ltd.

Haihe Biopharma Co., Ltd.

Shanghai Institute of Materia Medica Chinese Academy of Sci

+ [1]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (07 Mar 2023),

MET Exon 14 Skipping Mutation Non-small Cell Lung Cancer

RegulationConditional marketing approval (CN), Special Review Project (CN), Orphan Drug (US), Priority Review (CN), Breakthrough Therapy (CN)

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Structure

Molecular FormulaC21H17N9O2S

InChIKeyRYBLECYFLJXEJX-UHFFFAOYSA-N

CAS Registry1642581-63-2

A Randomized, Controlled, Open-label Phase Ⅱ Study to Evaluate the Safety, Tolerability, and Efficacy of the Combination of Glumetinib Tablets and Docetaxel for Injection（Albumin Bound）Verse Docetaxel in the Treatment of Locally Advanced/Recurrent or Distant Metastasized Non-small Cell Lung Cancer Patients With MET Overexpression

This study consists of Stage 1 (including dose escalation and dose expansion) and Stage 2 (randomized controlled study). The main purpose of Stage 1 is to preliminarily evaluate the safety and tolerability of the combination of glumetinib Tablets and Docetaxel for Injection（Albumin Bound）(HB1801) in the treatment of MET-overexpressed non-small cell lung cancer (NSCLC); The main purpose of Stage 2 is to evaluate the efficacy of the combination of glumetinib tablets and HB1801 compared to glumetinib tablets monotherapy or docetaxel in the treatment of MET-expressed NSCLC.

Start Date01 Jul 2024

Sponsor / Collaborator

CSPC Zhongqi Pharmaceutical Technology (Tianjin) Co., Ltd.

NCT06452433 / Not yet recruitingPhase 2IIT

Gumarontinib Combined With Third-generation EGFR-TKI in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer With MET Amplification Following EGFR-TKI Treatment Failure.

This study evaluated the efficacy and safety of gumarontinib combined with third-generation EGFR-TKI in the treatment of locally advanced or metastatic NSCLC with MET amplification after first-line EGFR-TKI failure, without limiting the type of third-generation EGFR-TKI. The study was divided into 2 cohorts: Cohort 1 included patients with MET amplification after third-generation EGFR-TKI first-line therapy resistance, and cohort 2 included patients with MET amplification after first-generation EGFR-TKI first-line therapy resistance.

Start Date01 Jun 2024

Sponsor / Collaborator

Cancer Hospital Chinese Academy of Medical Sciences

100 Clinical Results associated with Glumetinib

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100 Translational Medicine associated with Glumetinib

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100 Patents (Medical) associated with Glumetinib

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98

Literatures (Medical) associated with Glumetinib

01 Dec 2024·European Journal of Medicinal Chemistry

Discovery of 7-(1-methyl-1H-pyrazol-4-yl)-1,6-naphthyridine derivatives as potent inhibitors of rearranged during transfection (RET) and RET solvent-front mutants for overcoming selpercatinib resistance

Article

Author: Wu, Junbo ; Gong, Yi ; Mo, Hanxuan ; Zhou, Huifang ; Tan, Shuguang ; Tang, Zishu ; An, Zhigang ; Zhuo, Linsheng ; Deng, Xinyu ; Zheng, Chenggong

Rearranged during transfection kinase (RET) inhibition has been considered a promising therapeutic approach for treatment of a variety of cancers. However, the clinical therapeutic benefits of the second-generation RET inhibitor selpercatinib are greatly compromised by acquired resistance mediated by solvent-front mutations (e.g., RET^G810 R/S/C). Herein, we report a class of 7-(1-methyl-1H-pyrazol-4-yl)-1,6-naphthyridine derivatives as potent RET and RET solvent-front mutant inhibitors for overcoming selpercatinib resistance. The representative compound 20p exhibited excellent in vitro inhibitory activities against solvent-front mutations (RET^G810R, RET^G810S, and RET^G810C) with low nanomolar range (IC₅₀ of 5.7-8.3 nM), which was 15-29-fold more potent than selpercatinib (IC₅₀ of 95.3-244.1 nM). Additionally, 20p exhibited acceptable pharmacokinetic properties with oral bioavailability of 30.4 %. Importantly, 20p exhibited highly impressive antitumor potency in both a Ba/F3-KIF5B-RET^WT-derived xenograft mouse model and a selpercatinib-resistant Ba/F3-KIF5B-RET^G810R-positive mutant xenograft mouse model. Overall, 20p represents a novel and promising drug lead for overcoming RET solvent-front mutation-based resistance to selpercatinib.

01 Sep 2024·International Journal of Clinical Oncology

PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs: approval selpercatinib for solid tumor with RET fusion, gumarontinib for non-small cell lung cancer with MET gene exon 14 skipping mutation, momelotinib for myelofibrosis, bexarotene for adult T-cell leukemia/lymphoma, valemetostat for peripheral T-cell lymphoma, and pirtobrutinib for mantle cell lymphoma in Japan

Article

Author: Matsumura, Noriomi ; Mandai, Masaki

12 Apr 2024·Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases

[Clinical characteristics and prognosis analysis of pulmonary sarcomatoid carcinoma].

Article

Author: Xu, Y ; Liu, X Y ; Chen, M J ; Wang, M Z ; Zhong, W ; Gao, X X ; Feng, X Y ; Zhao, J

Objective: To summarize the clinical characteristics, treatment, and outcomes of patients with pulmonary sarcomatoid carcinoma (PSC) in order to improve clinicians' understanding of this disease. Methods: The clinical data of patients diagnosed with PSC in our hospital from January 1, 2015 to November 30, 2023 were retrospectively analyzed. According to whether radical resection was performed, the patients were divided into resectable group and unresectable group. The characteristics and treatments of PSC in different groups were compared. The survival curves were drawn by Kaplan-Meier method to compare the prognosis of different groups of patients. Results: A total of 43 PSC patients were included, including 32 males, with an average age of (62.79±9.59) years, and 31 smokers. Peripheral-type tumors were more common, with imaging showing predominantly solid soft tissue masses, and the maximum diameter of the tumor was more than 5 cm in 14 patients. Among the 23 patients who underwent NGS gene testing, the KRAS mutation rate was 43.5%, the TP53 mutation rate was 30.4%, and the MET mutation rate was 8.7%, all of which were MET-14 exon skipping mutations. PD-L1 expression was detected in 13 patients, 10 of whom showed high expression. The median overall survival (mOS) of the 43 patients with PSC was 24.6 months (13.0-52.7 months). Among them, 22 patients underwent radical lobectomy plus mediastinal lymph node dissection, 13 patients had postoperative recurrence, and 7 patients died during follow-up. The median disease-free survival (mDFS) was 12.3 months, the mOS was not achieved and the 1-year OS rate was 77.3 %. Twenty-one patients had unresectable locally advanced or advanced stage, and 15 patients died. The mDFS was 2.5 months, the mOS was 6.2 months, and the 1-year OS rate was 42.9 %. Seventeen patients received immunotherapy, and 1 patient received targeted therapy with the MET inhibitor glumetinib. Conclusions: PSC has a higher incidence in the elderly, smokers, and males, is highly malignant and has a poor prognosis. Based on its molecular biological characteristics, PD-L1 expression and tumor molecular detection can be performed to guide treatment options.

100 Deals associated with Glumetinib

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15630

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
c-Met positive non-small cell lung cancer	JP	Haihe Biopharma Co., Ltd.	24 Jun 2024
MET Exon 14 Skipping Mutation Non-small Cell Lung Cancer	CN	Haihe Biopharma Co., Ltd.	07 Mar 2023

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Recurrent Non-Small Cell Lung Cancer	Phase 2	CN	Haihe Biopharma Co., Ltd.	18 Nov 2019
c-Met positive Adenocarcinoma of Esophagus	Phase 2	CN	Shanghai Green Valley Pharmaceutical Co., Ltd.	31 Jul 2019
c-Met positive Adenocarcinoma of Esophagus	Phase 2	CN	Shanghai Institute of Materia Medica Chinese Academy of Sci	31 Jul 2019
Advanced Lung Non-Small Cell Carcinoma	Phase 2	JP	Haihe Biopharma Co., Ltd.	15 Jul 2019
Advanced Lung Non-Small Cell Carcinoma	Phase 2	CN	Haihe Biopharma Co., Ltd.	15 Jul 2019
Advanced Lung Non-Small Cell Carcinoma	Phase 2	US	Haihe Biopharma Co., Ltd.	15 Jul 2019
c-Met positive non-small cell lung cancer	Phase 2	CN	Haihe Biopharma Co., Ltd.	15 Jul 2019
c-Met positive non-small cell lung cancer	Phase 2	US	Haihe Biopharma Co., Ltd.	15 Jul 2019
MET Exon 14 Skipping Mutation Non-small Cell Lung Cancer	Phase 2	US	Haihe Biopharma Co., Ltd.	15 Jul 2019
MET Exon 14 Skipping Mutation Non-small Cell Lung Cancer	Phase 2	JP	Haihe Biopharma Co., Ltd.	15 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


NCT04270591 \| NCT03457532 (Pubmed) Manual	Not Applicable	c-Met positive non-small cell lung cancer	32	Gumarontinib 300 mg QD	(scjzgelcdt) = gyntuyfhaj donbcrmjbk (zmlqpvuzsk, 63.6 - 92.8) View more	Positive	01 Jan 2024
NCT04270591 \| NCT03457532 (ESMO_ASIA2022) Manual	Phase 1	Non-Small Cell Lung Cancer	32	SCC244 300 mg	(adutxibqoq) = iztvgmirzh qqtjwogdsm (rulqqrtdyf, 21.1 - 56.3) View more	Positive	03 Dec 2022
NCT04270591 \| NCT03457532 (ESMO_ASIA2022) Manual	Phase 1	Non-Small Cell Lung Cancer	32	SCC244 300 mg (treatment naïve patients)	(adutxibqoq) = snuzsponfh qqtjwogdsm (rulqqrtdyf, 15.2 - 72.3)	Positive	03 Dec 2022
NCT04338243 (SCC244 plus osimertinib, ESMO_ASIA2022)	Phase 2	EGFR-mutated non-small Cell Lung Cancer	30	SCC244	(mzqezzloyl) = nlsvygusla twzwhvtdfr (mwqpnitjwi, [40.6 - 77.3]) View more	-	03 Dec 2022
NCT03466268 (ESMO_TAT2021)	Phase 1	Non-Small Cell Lung Cancer	19	SCC244	(zlbegerywf) = szmbnhdvhz ttwckzjbwh (dkqmlkaggy ) View more	-	01 Mar 2021
NCT03466268 (ASCO2020)	Phase 1	Advanced Lung Non-Small Cell Carcinoma	18	Glumetinib	qfumoetpbv(sbtesqdxvq) = Peripheral edema (n = 1, 5.5%), hypothyroidism (n = 1, 5.5%) uecvnwgryy (dyqpyqdzww ) View more	Positive	25 May 2020