Delving into the Latest Updates on Ensartinib Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Ensartinib, Ensartinib hydrochloride (USAN), 恩沙替尼

+ [5]

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 DiseasesSkin and Musculoskeletal Diseases

Active Indication

ALK positive Non-Small Cell Lung CancerMelanomaAdvanced Malignant Solid Neoplasm

Inactive Indication

Brain metastasesmetastatic non-small cell lung cancerReactive oxygen species 1 positive non-small cell lung cancer

Originator Organization

Xcovery, Inc.

Active Organization

Betta Pharmaceuticals Co., Ltd.

Xcovery Holding, Inc.

Inactive Organization

MedImmune LLC

Drug Highest PhaseApproved

First Approval Date

CN (17 Nov 2020),

ALK positive Non-Small Cell Lung Cancer

RegulationPriority Review (CN), Conditional marketing approval (CN)

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Structure/Sequence

Molecular FormulaC26H29Cl4FN6O3

InChIKeyIERUINQRGJAECT-ISUJJMBGSA-N

CAS Registry2137030-98-7

This umbrella trial directed by next generation sequencing (NGS) includes patients with treatment-naive unresectable stage III non-small-cell lung cancer (NSCLC). The aim of the umbrella study is to evaluate the efficacy of induction NGS-directed targeted therapies followed by surgery for stage III NSCLC patients whose tumor harbors a rare mutation.

Start Date01 Nov 2024

Sponsor / Collaborator

Sun Yat-Sen University

100 Clinical Results associated with Ensartinib Hydrochloride

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100 Translational Medicine associated with Ensartinib Hydrochloride

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100 Patents (Medical) associated with Ensartinib Hydrochloride

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118

Literatures (Medical) associated with Ensartinib Hydrochloride

01 Dec 2024·Asia-Pacific Journal of Clinical Oncology

Ensartinib in the treatment of anaplastic lymphoma kinase‐positive locally advanced or metastatic patients with lung squamous or adenosquamous carcinoma: A real‐world, retrospective study

Article

Author: Ji, Dong ; Yang, Min ; Yuan, Xiaobin ; Wang, Yang ; Ma, Yongbin ; Ding, Lieming ; Yun, Yu ; Chen, Hui ; Shen, Zhilin ; Wu, Pengxiang

Abstract:

Aim:

To report the efficacy and safety of ensartinib, an anaplastic lymphoma kinase (ALK) inhibitor, in treating patients with ALK‐positive advanced lung squamous cell carcinoma (LUSC) or lung adenosquamous carcinoma (LASC) in China.

Methods:

This retrospective study analyzed data for 36 advanced‐stage patients with ALK‐positive LUSC (cohort A) and 13 patients with ALK‐positive LASC (cohort B) between December 16, 2020 and December 16, 2021. All patients received once‐daily ensartinib 225 mg. Outcome analysis included the demographic characteristics, tumor response, progression‐free survival (PFS), and treatment‐related adverse events (TRAE).

Results:

Among the 49 patients, the majority were under 65 years old (73.5%), non‐smokers (85.7%), had an Eastern Cooperative Oncology Group Performance Status of 0–1 (77.6%), and were at stage IV (71.4%). All patients were included in the efficacy and safety analysis. Seven PFS events were reported in cohort A while no patients experienced PFS events in cohort B. The median PFS was not estimable for both cohorts. In cohort A, the objective response rate (ORR) was 63.9%, and the disease control rate (DCR) was 83.3%. In the cohort B, the ORR was 76.9% and the DCR was 100.0%. Rash was the only TRAE reported in the cohort A (8.3%) and cohort B (23.1%). No patients had grade 3 or higher TRAE.

Conclusion:

Ensartinib has been tentatively proven favorable efficacy and tolerability in the treatment of patients with ALK‐positive advanced LUSC or LASC in the real‐world. However, confirmatory studies are still needed in larger sample sizes.

01 Dec 2024·Clinical Respiratory Journal

Dramatic Response to Ensartinib in Metastatic Neuroendocrine Tumors With a Novel CEP44‐ALK Fusion: A Case Report and Literature Review

Review

Author: Wu, Xuan ; Chen, Haiyang ; Wang, Qiming ; Wang, Kai ; Wu, Yingxi ; Xia, Qingxin

ABSTRACT:

Neuroendocrine tumor (NET) is a deadly malignancy disease that can be found anywhere in the body. The lack of tumor‐specific treatment led to the worse prognosis of NET. Anaplastic lymphoma kinase‐tyrosine kinase inhibitors (ALK‐TKIs), such as alectinib and crizotinib, have been used in the treatment of NET patients with ALK rearrangement. However, the response to ensatinib in NET patients with rare ALK fusion has been rarely reported. Here, we report a 55‐year‐old Chinese female patient with NET (atypical carcinoid tumor) and a novel CEP44‐ALK rearrangement identified by next‐generation sequencing (NGS). NGS can provide more information on mutation landscape for rare neuroendocrine tumors to guide treatment and assist in clinical decisions by presenting molecular changes. The patient received ensartinib (225 mg/day) for 18 months until disease progression in June 2024 and achieved a radiographic partial response. Although patients with ALK fusions showed response to ensatinib in nonsmall cell lung cancer (NSCLC), this study first reports a metastatic NET case with a novel CEP44‐ALK rearrangement that responded favorably to ensartinib.

01 Oct 2024·Heliyon

Small intestinal metastasis in a lung adenocarcinoma patient with concurrent EML4-ALK V3 and TP53 mutations after distinct responses to tyrosine kinase inhibitors: A case report

Article

Author: Zhang, Yongqian ; Guo, Ying ; Ma, Wenhua ; Liu, Zhai ; Zhao, Min ; Lv, Hengxu ; Zhao, Yingchun ; Wang, Qian ; Zhu, Lingling ; Guo, Yan

Background:

Although anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have improved the survival rates of lung cancer patients with ALK fusion mutations, their effectiveness varies significantly across different subtypes. We report a case of small intestine metastasis in a lung adenocarcinoma patient with co-occurring echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variant 3 (V3) and tumor protein 53 (TP53) mutations after distinct responses to ALK-TKIs.

Case presentation:

A 45-year-old woman was diagnosed with stage IV lung adenocarcinoma with brain metastasis. Next-generation sequencing revealed EML4-ALK V3 and TP53 co-mutations. After the initial treatment with ensartinib, the patient experienced intracranial disease progression. Radiation therapy (RT) was then administered. Despite good response to RT for the intracranial disease, the primary tumor enlarged. Thus, the patient was treated with oral ensartinib concurrent with chemotherapy, with a partial response in both the primary tumor and intracranial metastases. However, after three cycles of treatment, the patient discontinued chemotherapy because of acute kidney injury. Subsequent thoracic RT resulted in a partial response of the primary tumor; however, new brain and bone metastases were detected, prompting a switch to lorlatinib. The patient developed symptoms of intestinal obstruction 14 months after the initial diagnosis. Surgical intervention revealed a poorly differentiated metastatic lung adenocarcinoma of the upper jejunum. Genetic testing confirmed EML4-ALK V3 and TP53 co-mutations and high expression of programmed cell death-ligand 1. Despite pembrolizumab treatment, the patient's condition deteriorated, and she passed away.

Conclusion:

We reported a rare case of small intestinal metastasis in a lung adenocarcinoma patient with concurrent EML4-ALK V3/TP53 mutations after distinct responses to ALK-TKIs in different lesions. Our findings revealed heterogeneity in ALK mutations and responses to ALK-TKIs, necessitating the close monitoring of genetic subtypes and associated mutations for tailored treatment strategies. Maintaining a heightened awareness of potential intestinal metastasis and vigilance in monitoring intestinal symptoms and abdominal metastases are pivotal for managing advanced lung adenocarcinoma.

12

News (Medical) associated with Ensartinib Hydrochloride

24 Dec 2024

·www.echemi.com

Novo Nordisk Announces 68-Week Weight Loss Data from REDEFINE 1 Clinical Trial

Recently, Novo Nordisk announced the efficacy and safety data from its semaglutide and Cagrilintide combination therapy in the weight loss domain from the Phase III clinical trial REDEFINE 1. This clinical trial recruited 3,417 obese or overweight patients, each with at least one weight-related risk factor. After 68 weeks of treatment, 57.3% of patients in the CagriSema treatment group reached the highest dose. In comparison, 82.5% and 70.2% of patients in the Cagrilintide and semaglutide monotherapy groups reached the highest dose, respectively. Regarding weight loss efficacy, the weight loss percentages after 68 weeks of treatment were 22.7%, 11.8%, 16.1%, and 2.3% for CagriSema, Cagrilintide, semaglutide, and the placebo group, respectively. Compared to the placebo, the weight loss amounts during the 68 weeks were 20.4%, 9.5%, and 13.8% for CagriSema, Cagrilintide, and semaglutide, respectively. Currently, CagriSema is undergoing five Phase III clinical trials, one of which, REDEFINE 4, will directly compare it with tirzepatide. Novo Nordisk hopes that CagriSema can achieve weight loss effects comparable to tirzepatide. Previously, CagriSema achieved a 17% weight loss effect over 20 weeks in Phase I trials and a 15.6% weight loss effect over 32 weeks in Phase II trials targeting patients with diabetes and overweight. Novo Nordisk previously anticipated that the Phase III clinical trials could achieve a weight loss of at least 25%. Additionally, Betta Pharmaceuticals' ALK inhibitor ensartinib has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ALK-positive locally advanced or metastatic non-small cell lung cancer, marketed under the name Ensacove. This approval is based on the data from the eXALT3 clinical trial, which directly compared ensartinib with crizotinib. The primary endpoint was progression-free survival (PFS), and the key secondary endpoint was overall survival (OS). The median progression-free survival (mPFS) for ensartinib and crizotinib was 25.8 months and 12.7 months, respectively, reducing the risk of disease progression or death by 44%. There was no significant difference in overall survival between the two groups, with a hazard ratio (HR) of 0.88. In terms of safety, the most common side effects included rash, musculoskeletal pain, constipation, cough, itching, nausea, edema, fever, and fatigue.

Clinical ResultPhase 2Phase 3Drug ApprovalPhase 1

19 Dec 2024

·endpts.com

Xcovery nabs first FDA approval for lung cancer drug

The FDA has approved Xcovery Holdings’ ALK inhibitor Ensacove for first-line treatment of adults with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer. The approval late Wednesday was based on a trial of 290 patients with the disease who had not previously received an ALK-targeted therapy. In a trial, according to the FDA, Ensacove demonstrated a statistically significant progression-free survival improvement compared to Pfizer’s Xalkori. However, there wasn’t a statistically significant difference in overall survival (p=0.4570). It’s Xcovery’s first FDA approval, and Ensacove, also known as ensartinib, is also in development for other cancers. The company is also working on vorolanib, a multi-kinase inhibitor in combo with other compounds like everolimus. Xcovery did not immediately respond to a request for comment on Ensacove’s price.

Drug ApprovalAccelerated ApprovalADCImmunotherapy

19 Dec 2024

·pipelinereview.com

FDA Approval of Ensartinib for ALK-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

MIAMI, FL, USA I December 18, 2024 I Xcovery Holdings, Inc. , an oncology focused pharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has approved ensartinib (Ensacove, Xcovery Holdings, Inc.) for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). This approval marks an important advancement in providing a new first line option for patients with ALK-positive NSCLC. Ensartinib is an ALK tyrosine kinase inhibitor (TKI) designed to improve outcomes for patients with ALK-positive NSCLC. The FDA approval is based on data from the pivotal global Phase III eXalt3 clinical trial, in which ensartinib demonstrated statistically significant improvements in progression-free survival (PFS) over crizotinib. “The approval of Ensartinib by FDA brings another new medicine to patients battling ALK-positive NSCLC, expanding the options to optimize treatment in the first-line setting. This result could not have been achieved without the dedication of our team members and the support of patients, physicians, and all stakeholders involved in the clinical development of Ensartinib,” said Giovanni Selvaggi, Chief Medical Officer of Xcovery. “FDA approval of Ensartinib represents a significant milestone in Xcovery’s mission to advance precision medicine for patients with cancer,” said Kevin Sang, CEO of Xcovery. “In addition to Ensartinib, we are continuing our efforts in developing more pipeline targeted drugs for patients worldwide.” About Ensartinib Ensartinib is a next generation ALK inhibitor jointly developed by Xcovery and Betta Pharmaceuticals. It is indicated for the treatment of adult patients with ALK-positive locally advanced or metastatic NSCLC. About Xcovery Xcovery is a pharmaceutical company working to improve the lives of patients with cancer by discovering and developing small molecules that precisely target cancer growth mechanisms. Xcovery is developing a pipeline of drugs targeting a wide range of advanced solid tumors with a focus on lung cancer. SOURCE: Xcovery

Drug ApprovalPhase 3Clinical Result

100 Deals associated with Ensartinib Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D11356	-	L01XE	DB14860

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
ALK positive Non-Small Cell Lung Cancer	CN	Betta Pharmaceuticals Co., Ltd.	17 Nov 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Brain metastases	Phase 2	CN	Betta Pharmaceuticals Co., Ltd.	21 Mar 2019
Reactive oxygen species 1 positive non-small cell lung cancer	Phase 2	CN	Betta Pharmaceuticals Co., Ltd.	29 May 2018
Melanoma	Phase 2	US	Xcovery Holding, Inc.	10 Jan 2018
Advanced Malignant Solid Neoplasm	Phase 2	US	Xcovery Holding, Inc.	01 Jun 2012
Lung Cancer	Phase 1	CN	Betta Pharmaceuticals Co., Ltd.	11 Jun 2018
metastatic non-small cell lung cancer	Phase 1	CN	Betta Pharmaceuticals Co., Ltd.	06 Mar 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02767804 (eXALT3, FDA_CDER) Manual	Phase 3	ALK positive Non-Small Cell Lung Cancer ALK Positive	290	ENSACOVE	cxwpacqeng(adrbkxqxqm) = lanrqjnrrx mmvhrqvzuc (wdtsukuraa, 21.8 - NE) View more	Positive	18 Dec 2024
				Crizotinib	cxwpacqeng(adrbkxqxqm) = kwmrlwjqij mmvhrqvzuc (wdtsukuraa, 9.2 - 16.6) View more
ChiCTR2100048767 (WCLC2024) Manual	Phase 2	MET Exon 14 Skipping Mutation Non-small Cell Lung Cancer MET Exon 14 Skipping	30	Ensartinib 225 mg	zhhjazezyh(awtatotfyd) = pnzmzjcjwy olgtmclfdv (nxkibahrjw, 36.1% - 69.8) View more	Positive	10 Sep 2024
NCT03215693 (Literature) Manual	Phase 2	ALK positive Non-Small Cell Lung Cancer ALK Positive \| TP53 Mutation	180	Ensartinib 225 mg	hqrccqmtqp(luqmckjkeb) = alccqvryrq suzywpnfoq (fxnryvlidj, 29.3 - 53.2) View more	Positive	29 Feb 2024
NCT02959619 (Pubmed)	Phase 1	ALK positive Non-Small Cell Lung Cancer	48	Ensartinib	tykwonofpv(krjfkujclr) = 4.2% xojnxxyrjn (oklcrkzqcf ) View more	-	01 Dec 2022
WCLC2022	Not Applicable	-	-	Crizotinib	jsfepnjdut(sdaxnrjvim) = mcofcivqgv ocbnovcvpr (vouegxffua )	-	06 Aug 2022
				Alectinib	jsfepnjdut(sdaxnrjvim) = kmfpjqkgzg ocbnovcvpr (vouegxffua )
NCT03215693 (WCLC2022)	Phase 2	-	-	Ensartinib (ALK Fusion Subtype Variant 1 (V1))	cyaxgajwan(pkdjhklfge) = vjnzfstvzk ayatjvyyii (nwobgddtsa ) View more	-	06 Aug 2022
				Ensartinib (ALK Fusion Subtype Variant 3 (V3))	cyaxgajwan(pkdjhklfge) = dteblyuabd ayatjvyyii (nwobgddtsa ) View more
NCT02767804 (eXalt3, Pubmed \| JAMA Oncol) Manual	Phase 3	ALK positive Non-Small Cell Lung Cancer First line ALK Positive	290	Ensartinib Hydrochloride	irrxryuezr(sdgmdqpnmc) = cukturouvs asvudtwjjy (gchjosgrsl ) View more	Superior	01 Nov 2021
				Crizotinib	irrxryuezr(sdgmdqpnmc) = rxzrlirqpx asvudtwjjy (gchjosgrsl ) View more
NCT03608007 (Pubmed) Manual	Phase 2	Reactive oxygen species 1 positive non-small cell lung cancer ROS1 Positive	59	Ensartinib	vttdrypuew(kqfqftniey) = ruqabxdtsi krijprhfkh (xvlkqclzbn, 13.8 - 44.1) View more	Positive	01 Nov 2021
WCLC2021	Not Applicable	-	178	Ensartinib (ALK-EML4 V1 subtype)	vvbshmubno(ywpfthtcwy) = cmcwbpfyyf pdqpxcnzpv (atittzdmgc )	-	08 Sep 2021
				Ensartinib (ALK-EML4 V3 subtype)	vvbshmubno(ywpfthtcwy) = liarojftqz pdqpxcnzpv (atittzdmgc )
NCT03804541 (Pubmed \| Cancer Chemother Pharmacol)	Phase 1	-	6	Ensartinib 200 mg/100 μCi	lyckwzesou(ulaoqqadyg) = vslzxyjofv lcptbpeyeo (cbqdaenxos ) View more	-	01 Dec 2020