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(Abstract)

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This abstract discusses a study on acquired resistance to the drug mobocertinib in the treatment of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Currently, EGFR-tyrosine kinase inhibitors (TKIs) are not effective for this specific group of patients. The study examined the efficacy of mobocertinib and other EGFR-TKIs in cell models with different EGFR exon 20 insertion mutations. Mobocertinib showed the highest efficacy compared to other TKIs in all cell models, including the less sensitive H773_V774insH mutation. The study also explored the on-target acquired resistance mechanisms to mobocertinib by establishing resistant cell clones and identified secondary mutations such as T790M or C797S. The results showed that sunvozertinib could potentially be effective against cells with T790M mutation, while cytotoxic chemotherapy may be a consideration for patients with the C797S mutation.Overall, the findings suggest that acquired resistance to mobocertinib in NSCLC with EGFR exon 20 mutations is caused by specific secondary mutations depending on the original activating mutations. The study highlights the need for further treatment strategies for patients who develop these resistance mutations.

Asset Subtitle

Akira Hamada

Meta Tag

Speaker Akira Hamada

Topic Tumor Biology: Translational Biology - Drug Resistance

Keywords

acquired resistance

mobocertinib

non-small cell lung cancer

NSCLC

epidermal growth factor receptor

EGFR

exon 20 insertion mutations

EGFR-tyrosine kinase inhibitors

efficacy

cell models