Delving into the Latest Updates on Oritinib Mesylate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

甲磺酸瑞厄替尼

+ [1]

Target

EGFR L858R x EGFR T790M x EGFR-Ex19del

Mechanism

EGFR T790M inhibitors(EGFR T790M inhibitors), EGFR exon 19 deletion inhibitors, EGFR exon 21 L858R mutation inhibitors

Therapeutic Areas

NeoplasmsRespiratory Diseases

Active Indication

EGFR positive non-small cell lung cancerEGFR T790M Mutation Positive Non-Small Cell Lung CarcinomaLocally Advanced Lung Non-Small Cell Carcinoma

Inactive Indication

Advanced Lung Non-Small Cell CarcinomaAdvanced Malignant Solid NeoplasmEGFR-mutated non-small Cell Lung Cancer

Originator Organization

Nanjing Sanhome Pharmaceutical Co. Ltd.

Active Organization

Nanjing Sanhome Pharmaceutical Co. Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (11 Jun 2024),

EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma

RegulationSpecial Review Project (CN)

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This is a phase I study to assess the drug-drug interaction of SH-1028 tablets and Itraconazole/Rifampicin tablets. The study also evaluates the pharmacokinetic and tolerability of SH-1028 tablets in healthy subjects. This study provides evidence for the designing of following clinical trial protocols.

Start Date06 Apr 2021

Sponsor / Collaborator

Nanjing Sanhome Pharmaceutical Co. Ltd.

100 Clinical Results associated with Oritinib Mesylate

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100 Translational Medicine associated with Oritinib Mesylate

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100 Patents (Medical) associated with Oritinib Mesylate

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6

Literatures (Medical) associated with Oritinib Mesylate

31 Oct 2023·Zhonghua yi xue za zhi

[China clinical practice guideline for epidermal growth factor receptor tyrosine kinase inhibitors in stage Ⅳ non-small cell lung cancer (version 2023)].

Article

The incidence and mortality of lung cancer rank first among malignant tumors in China. Among them, non-small cell lung cancer (NSCLC) is the most important pathological type, accounting for 80%-85% of lung cancer patients, including adenocarcinoma, squamous cell carcinoma and other pathological subtypes. In recent years, with the discovery of epidermal growth factor receptor (EGFR) gene and the successful development of tyrosine kinase inhibitors (TKIs), the treatment efficacy of stage Ⅳ NSCLC patients with EGFR gene sensitive mutation has been greatly improved. As of August 23, 2023, the first generation EGFR-TKIs, gefitinib, icotinib, and erlotinib; the second generation EGFR-TKIs, afatinib and dacomitinib; and the third generation EGFR-TKIs, osimertinib, almonertinib, furmonertinib and befotertinib were all approved for marketing by China National Medical Products Administration (NMPA). In addition, multiple domestic third-generation EGFR-TKIs are undergoing clinical trials, such as rezivertinib (BPI-7711), limertinib (ASK120067), and oritinib (SH-1028). Meanwhile, mobocertinib and sunvozertinib, which targets EGFR 20ins mutations, were also approved by NMPA. With the increasing variety of EGFR-TKIs approved for marketing subsequently, it brings confusion to clinicians when choosing specific medications, and there is an urgent need to develop relevant treatment guidelines. Hence, the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Chinese Association for Clinical Oncologists convened experts to integrate the research results of various EGFR-TKIs, and proposed the "China clinical practice guideline for epidermal growth factor receptor tyrosine kinase inhibitors in stage Ⅳ non-small cell lung cancer (version 2023)", to provide reference for better clinical practice.

01 Jun 2023·Investigational new drugs

Drug-drug interaction potential of SH-1028, a third-generation EGFR-TKI: in vitro and clinical trials

Article

Author: Wang, Ying ; Liu, Bingyan ; Zhu, Minhui ; He, Cuixia ; Xie, Jing ; Liu, Yuyan ; Zhou, Huan ; Xu, Yuanyuan ; Shan, Rongfang ; Liu, Yuanyuan ; Li, Xiaoli ; Ding, Jiaxiang ; Ding, Yuzhou ; Wang, Zhiqiang

SH-1028 is an irreversible third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). Considering the possibility of combination therapy in patients with NSCLC, we investigated the drug-drug interaction (DDI) potential of SH-1028 both in vitro and in clinical trials. The in vitro studies were conducted to determine the potential of SH-1028 as a substrate, inducer, or inhibitor of cytochrome P450 (CYP) subtypes. A phase I drug-drug interaction study in healthy volunteers was performed to evaluate the impact of co-administering rifampicin (a strong CYP3A4 inducer) and itraconazole (a strong CYP3A4 inhibitor) on the pharmacokinetics of SH-1028. The in vitro experiments showed that SH-1028 was mainly metabolized by CYP3A4. The activities of CYP1A2, 2B6, 2C19, 2D6 and 3A4 enzymes were slightly inhibited in vitro with SH-1028. SH-1028 has no obvious induction effect on CYP1A2 and CYP2B6 activities, but has potential induction effect on CYP3A4 mRNA expression. However, SH-1028 may not induce or inhibit human CYPs significantly at the clinically expected dose (200 mg). The geometric mean ratios of pharmacokinetic parameters and their corresponding 90% confidence intervals for SH-1028 in combination and alone did not fall within the range of 80-125%. It is speculated that itraconazole and rifampicin affect the metabolism of SH-1028. In the clinical application of SH-1028, special attention should be paid to the interaction between SH-1028 and drugs or foods that affect the activity of CYP3A4. (Clinical trial registration number: CTR20210558).

15 May 2023·Cancer

Safety, efficacy, and pharmacokinetics of SH‐1028 in EGFR T790M‐positive advanced non–small cell lung cancer patients: A dose‐escalation phase 1 study

Article

Author: Shi, Xinsheng ; He, Jing ; Gao, Wen ; Zhao, Dongmei ; Shu, Yongqian ; Ma, Pei ; Guo, Renhua

AbstractBackgroundSH‐1028 is a new third‐generation EGFR tyrosine kinase inhibitors (TKI) to benefit patients with EGFR T790M‐mutated NSCLC. Here, the authors report its clinical safety, preliminary efficacy, and pharmacokinetic (PK) profile for the first time.MethodsPatients with EGFR T790M mutation, locally advanced non–small cell lung cancer (NSCLC), or metastatic NSCLC who had progressed after previous EGFR TKI therapy were eligible. Patients received SH‐1028 at five oral dose levels (60 mg, 100 mg, 200 mg, 300 mg, and 400 mg) once daily until disease progression, unacceptable toxicity, or patient withdrawal. The primary end points were the safety, dose‐limiting toxicity (DLT), maximum‐tolerated dose (MTD), and PK profile. Secondary end points included objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), etc.ResultsData cut off on December 31, 2020, a total of 20 patients were enrolled during the trial, two of three patients in 300 mg cohort experienced a DLT, and no DLT was observed in 240 mg cohort, 240 mg was determined to be the MTD of SH‐1028. A total of 95.0% (19 of 20) of patients reported treatment‐related adverse events (TRAEs), and the incidence of serious adverse events was 20.0% (4 of 20). The ORR and DCR of the 200 mg cohort were 75% (95% confidence interval [CI], 19.41–99.37) and 75.0% (95% CI, 19.41–99.37), respectively. The overall ORR was 40% (95% CI, 19.12–63.95), and DCR was 70.0% (95% CI, 45.72–88.11). According to the PK profile, the dosage regimen for future studies was determined as 200 mg once daily.ConclusionsSH‐1028 showed a manageable safety and promising antitumor activity in patients with EGFR T790M mutation at the dose of 200 mg once daily.Plain language summary

Lung cancer has a high morbidity and mortality, with an estimated 1.8 million deaths in 2020. Non–small cell lung cancer accounts for approximately 85% of lung cancer.

First‐ or second‐generation EGFR TKIs' weak selectivity often led to the occurrence of treatment‐related adverse events, such as interstitial lung disease, rash, diarrhea, etc., along with acquired drug resistance within approximately 1 year.

A dose of 200 mg of SH‐1028 once daily showed a preliminary antitumor activity with manageable safety in patients with EGFR T790M mutation.

100 Deals associated with Oritinib Mesylate

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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
EGFR positive non-small cell lung cancer	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	09 Sep 2024
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	11 Jun 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 1	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	24 Mar 2021
EGFR positive non-small cell lung cancer	Preclinical	-	Nanjing Sanhome Pharmaceutical Co. Ltd.	31 Jan 2020
EGFR-mutated non-small Cell Lung Cancer	Preclinical	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	11 Jul 2019
Advanced Malignant Solid Neoplasm	Preclinical	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	13 Sep 2018
Advanced Lung Non-Small Cell Carcinoma	Preclinical	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	25 Apr 2018
metastatic non-small cell lung cancer	Discovery	-	Nanjing Sanhome Pharmaceutical Co. Ltd.	31 Jan 2020

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04239833 (WCLC2024) Manual	Phase 3	EGFR positive non-small cell lung cancer First line	245	Rilertinib 200 mg	(cheuhavjff) = saynashiur khkmukwent (nsrnusisjs, 15.2 - 22.3) View more	Positive	08 Sep 2024
				Gefitinib 250 mg	(cheuhavjff) = knxwfcitdv khkmukwent (nsrnusisjs, 7.1 - 12.6) View more
NCT04239833 (SHC013-III-01, NEWS) Manual	Phase 3	metastatic non-small cell lung cancer \| Locally Advanced Lung Non-Small Cell Carcinoma First line EGFR敏感突变	227	甲磺酸瑞厄替尼片	(kpqsdwextl) = sdvztxijpv rvmngxeikg (pgypltktwr ) Met	Positive	17 Jun 2024
				吉非替尼	(kpqsdwextl) = iwmkyhzgpt rvmngxeikg (pgypltktwr ) Met
NCT03823807 (Pubmed) Manual	Phase 2	EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma Second line EGFR T790M positive	286	SH-1028 (dose verification study)	(hzqpjvxlyl) = vwqyweaeuo nwmxspjikn (dabfdjidiq, 42.4 - 68.8) View more	Positive	04 Jul 2022
				SH-1028 (second-line registration study)	(hzqpjvxlyl) = aygllbsrie nwmxspjikn (dabfdjidiq, 53.7 - 66.8) View more
NCT03823807 (ESMO_ELCC2022)	Phase 2	EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma \| Non-Small Cell Lung Cancer	227	Oritinib 200 mg	(jtcsqhouhr) = pmiszfmrrk zakdmumrif (wehkkwectq, 42.4% - 68.8%) View more	-	30 Mar 2022
NCT03603262 (Pubmed) Manual	Phase 1	EGFR-mutated non-small Cell Lung Cancer EGFR T790M Mutation	20	SH-1028	(uvbvcegyxh) = 3 patients at 300 or 400mg dose, all of DLTs were increased blood creatine phosphokinase osskpwlsij (hcviqggmgy ) View more	Positive	25 Sep 2021
NCT03603262 (CSCO2021)	Phase 1	EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	20	SH-1028 (Oritinib) 60mg	(fsvpgqpwhx) = javflnioog psdhkipmym (vrcxuuoaxn, 19.12 - 63.95) View more	-	25 Sep 2021
				SH-1028 (Oritinib) 100mg	(fsvpgqpwhx) = ykmsjhxnhx psdhkipmym (vrcxuuoaxn, 19.12 - 63.95) View more
NCT03823807 (WCLC2021) Manual	Phase 1	EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma EGFR T790M Mutation	60	Oritinib	(dsjlxnfses) = fkpaodzkio fhgbfrivps (xuytrebqtl, 48.2 - 73.8) View more	Positive	08 Sep 2021