2023 World Conference on Lung Cancer (Posters)-P2.09. JIN-A04, Highly Effective and Brain-penetrant Tyrosine Kinase Inhibitor Targeting HER2 Exon20 Insertion Mutations in NSCLC

P2.09. JIN-A04, Highly Effective and Brain-penetrant Tyrosine Kinase Inhibitor Targeting HER2 Exon20 Insertion Mutations in NSCLC - PDF(Slides)

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This study focuses on the development of a tyrosine kinase inhibitor called JIN-A04, which targets HER2 exon20 insertion mutations in non-small cell lung cancer (NSCLC). NSCLC is the most common type of lung cancer, and around 2-4% of patients with NSCLC have mutations in the HER2 gene, with exon20 insertions being the most common type of mutation.<br /><br />The study aimed to investigate the efficacy of JIN-A04 in inhibiting cell viability and tumor growth in NSCLC cell lines engineered to express HER2 exon20 insertion mutations. The results showed that JIN-A04 demonstrated strong inhibitory activity against these cell lines, while sparing normal cell lines. It effectively inhibited downstream signaling pathways associated with these mutations.<br /><br />In in vivo studies using mouse models, JIN-A04 exhibited significant antitumor activity and tumor regression at various dose levels. It was also found to have intracranial activity in a model of brain metastases, reducing tumor volume in the brain.<br /><br />Overall, these findings suggest that JIN-A04 has the potential to be a highly effective and brain-penetrant drug candidate for NSCLC patients with HER2 exon20 insertion mutations. It demonstrates strong inhibitory activity, both in vitro and in vivo, and shows promise in addressing the limited treatment options for NSCLC patients with brain metastases.<br /><br />This study was funded by J INTS BIO Company, which had reviewed and provided feedback on the research. The authors had full editorial control and final approval of the content. The findings were presented at the IASLC 2023 WCLC conference.

Asset Subtitle

Mi Ra Yu

Meta Tag

Speaker Mi Ra Yu

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

tyrosine kinase inhibitor

JIN-A04

HER2 exon20 insertion mutations

non-small cell lung cancer

NSCLC

cell viability

tumor growth

inhibitory activity

signaling pathways

mouse models