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DRUG:

limertinib (ASK120067)

i
Other names: ASK120067, ASK-120067
Company:
Aosaikang Pharma, Innovent Biologics
Drug class:
EGFR inhibitor
Related drugs:
3ms
Branched-chain amino acid transaminase 1 confers EGFR-TKI resistance through epigenetic glycolytic activation. (PubMed, Signal Transduct Target Ther)
In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC.
Journal
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BCAT1 (Branched Chain Amino Acid Transaminase 1 )
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Tagrisso (osimertinib) • limertinib (ASK120067)
5ms
ASK120067 Versus Gefitinib as First-line Treatment for EGFRm Locally Advanced or Metastatic NSCLC (clinicaltrials.gov)
P3, N=337, Active, not recruiting, Jiangsu Aosaikang Pharmaceutical Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Sep 2026 | Trial primary completion date: Mar 2023 --> Mar 2024
Enrollment closed • Trial completion date • Trial primary completion date • Metastases
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gefitinib • limertinib (ASK120067)
6ms
AM-DMF-SCP: Integrated Single-Cell Proteomics Analysis on an Active Matrix Digital Microfluidic Chip. (PubMed, JACS Au)
Applying the AM-DMF-SCP to characterize the proteomes of a third-generation EGFR inhibitor, ASK120067-resistant cells (67R) and their parental NCI-H1975 cells, we observed a potential correlation between elevated VIM expression and 67R resistance, which is consistent with the findings from bulk sample analyses. These results suggest that AM-DMF-SCP is an automated, robust, and sensitive platform for single-cell proteomics and demonstrate the potential for providing valuable insights into cellular mechanisms.
Journal
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VIM (Vimentin)
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limertinib (ASK120067)
1year
China clinical practice guideline for epidermal growth factor receptor tyrosine kinase inhibitors in stage Ⅳ non-small cell lung cancer (version 2023) (PubMed, Zhonghua Yi Xue Za Zhi)
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.
Clinical guideline • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation
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Tagrisso (osimertinib) • erlotinib • Gilotrif (afatinib) • gefitinib • Conmana (icotinib) • Ameile (aumolertinib) • Vizimpro (dacomitinib) • Ivesa (firmonertinib) • Exkivity (mobocertinib) • Semena (befotertinib) • sunvozertinib (DZD9008) • Rui Bi Da (rezivertinib) • Sanrisso (rilertinib) • limertinib (ASK120067)
over1year
Design, Synthesis, and Evaluation of (R)-8-((Tetrahydrofuran-2-yl)methyl)pyrido[2,3-d]pyrimidin-7-ones as Novel Selective ACK1 Inhibitors to Combat Acquired Resistance to the Third-Generation EGFR Inhibitor. (PubMed, J Med Chem)
Activated Cdc42-associated kinase 1 (ACK1) alterations have been considered to mediate bypass acquired resistance to the third-generation EGFR inhibitors (ASK120067 and osimertinib) in NSCLC. In the ASK120067-resistant lung cancer cell line (67R), 10zi dose-dependently inhibited the phosphorylation of ACK1 and downstream AKT pathway and showed a strong synergistic anti-tumor effect in combination with ASK120067 in vitro. Additionally, 10zi also exhibited reasonable PK profiles with an oral bioavailability of 19.8% at the dose of 10 mg/kg, which provided a promising lead for further development of new anticancer drugs.
Preclinical • Journal
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CDC42 (Cell Division Cycle 42)
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Tagrisso (osimertinib) • limertinib (ASK120067)
almost2years
ASK120067 potently suppresses B-cell or T-cell malignancies in vitro and in vivo by inhibiting BTK and ITK. (PubMed, Front Pharmacol)
Oral administration of ASK120067 led to significant tumor regression in B-cell lymphoma and T-cell leukemia xenograft models by weakening Bruton's tyrosine kinase and interleukin-2-inducible T cell kinase signaling, respectively. Taken together, our studies demonstrated that ASK120067 exerted preclinical anti-tumor activities against B-/T-cell malignancy by targeting BTK/ITK.
Preclinical • Journal
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IL2 (Interleukin 2) • ITK (IL2 Inducible T Cell Kinase)
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limertinib (ASK120067)
2years
Journal
|
EGFR (Epidermal growth factor receptor)
|
Ameile (aumolertinib) • Ivesa (firmonertinib) • Lazcluze (lazertinib) • Semena (befotertinib) • Rui Bi Da (rezivertinib) • Sanrisso (rilertinib) • limertinib (ASK120067)
over2years
Efficacy and safety of Limertinib (ASK120067) in patients with locally advanced or metastatic EGFR T790M mutated non-small cell lung cancer: a multicenter, single-arm, phase 2b study. (PubMed, J Thorac Oncol)
Limertinib (ASK120067) demonstrated promising efficacy and an acceptable safety profile for the treatment of patients with locally advanced or metastatic EGFR T790M mutated NSCLC.
P2b data • Journal
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EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR T790M
|
limertinib (ASK120067)
over2years
ASK120067 Versus Gefitinib as First-line Treatment for EGFRm Locally Advanced or Metastatic NSCLC (clinicaltrials.gov)
P3, N=334, Recruiting, Jiangsu Aosaikang Pharmaceutical Co., Ltd. | Trial completion date: Aug 2021 --> Dec 2023 | Trial primary completion date: Jan 2021 --> Mar 2023
Trial completion date • Trial primary completion date
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EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion
|
gefitinib • limertinib (ASK120067)
over2years
Efficacy and safety of ASK120067 (limertinib) in patients with locally advanced or metastatic EGFR T790M-mutated non–small cell lung cancer: A multicenter, single-arm, phase IIb study. (ASCO 2022)
ASK120067 demonstrated promising efficacy and an acceptable safety profile for the treatment of patients with locally advanced or metastatic EGFR T790M mutated NSCLC.
Clinical • P2b data
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR T790M
|
limertinib (ASK120067)
almost4years
Development of an LC-MS/MS method for quantifying ASK120067, a novel mutant-selective inhibitor of the epidermal growth factor receptor (EGFR) as well as its main metabolite in human plasma and its application in a pharmacokinetic study. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci)
Further stabilities for the two analytes and internal standard were also investigated covered the entire experimental process beginning from harvesting whole blood to plasma extraction and analysis. ASK120067 was then administered without issue onto a dose-escalation, the first-in-human Phase I clinical trial in Chinese NSCLC patients to determine the pharmacokinetics of oral ASK120067 administration.
PK/PD data • Journal
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EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR T790M
|
limertinib (ASK120067)
4years
Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of ASK120067 in Locally Advanced and Metastatic Non Small Cell Lung Cancer (clinicaltrials.gov)
P1/2, N=507, Recruiting, Jiangsu Aosaikang Pharmaceutical Co., Ltd. | N=135 --> 507 | Trial completion date: Aug 2020 --> Aug 2021 | Trial primary completion date: Jan 2020 --> Jan 2021
Clinical • Enrollment change • Trial completion date • Trial primary completion date
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EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X
|
limertinib (ASK120067)
5years
Clinical • New P1/2 trial
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X
|
limertinib (ASK120067)