2023 World Conference on Lung Cancer (Posters)-P1.08. On-Target Acquired Resistance to Mobocertinib and Strategy to Overcome It - In Vitro Study Using EGFR Ex20 Insertion Models

P1.08. On-Target Acquired Resistance to Mobocertinib and Strategy to Overcome It - In Vitro Study Using EGFR Ex20 Insertion Models - PDF(Slides)

Back to course

Pdf Summary

Researchers from Kindai University Faculty of Medicine in Japan conducted an in vitro study to investigate the acquired resistance to the EGFR inhibitor, mobocertinib, as well as strategies to overcome it. Mobocertinib is an oral therapy approved for patients with EGFR Exon20 Insertion non-small cell lung cancer (NSCLC). The study also explored the efficacy of other promising tyrosine kinase inhibitors (TKIs) for NSCLC patients with EGFR Exon20 Insertion.<br /><br />The researchers used murine pro-B-cell line (Ba/F3) models to examine the efficacy of mobocertinib and other EGFR-TKIs against five common EGFR exon 20 insertion mutations. They then established resistant clones through chronic drug exposure and identified secondary resistance mutations. The results showed that mobocertinib had the highest efficacy against all Ba/F3 cells, including those with the less sensitive H773_V774insH mutation.<br /><br />For mobocertinib-resistant Ba/F3 cells, secondary mutations such as T790M or C797S were observed depending on the original EGFR exon 20 insertion. The emergence of T790M was more frequent in cells treated with lower drug concentrations. The study also evaluated the efficacy of other TKIs against the acquired resistant cells with secondary mutations.<br /><br />Based on their findings, the researchers concluded that T790M or C797S mutations could cause acquired resistance to mobocertinib in NSCLCs with EGFR exon 20 mutations. They suggested that sunvozertinib may be effective against acquired resistant cells with T790M mutation, but other treatment strategies, such as cytotoxic chemotherapy, should be considered for patients who develop C797S secondary mutation.<br /><br />In summary, this study provides insights into the acquired resistance mechanisms to mobocertinib and explores potential strategies to overcome it. The findings highlight the importance of understanding resistance mechanisms and developing alternative treatment approaches for patients with EGFR Exon20 Insertion NSCLC.

Asset Subtitle

Akira Hamada

Meta Tag

Speaker Akira Hamada

Topic Tumor Biology: Translational Biology - Drug Resistance

Keywords

Kindai University Faculty of Medicine

in vitro study

acquired resistance

EGFR inhibitor

mobocertinib

oral therapy

EGFR Exon20 Insertion

non-small cell lung cancer

tyrosine kinase inhibitors

NSCLC patients