2023 World Conference on Lung Cancer (Posters)-P2.09. VRN110755, A New Therapeutic Option for EGFR Mutation-Driven NSCLC with Brain Metastasis or 1st-line Osimertinib-Resistant EGFR Mutations

P2.09. VRN110755, A New Therapeutic Option for EGFR Mutation-Driven NSCLC with Brain Metastasis or 1st-line Osimertinib-Resistant EGFR Mutations - PDF(Slides)

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VRN110755 is a new therapeutic option for non-small cell lung cancer (NSCLC) that is driven by EGFR mutations and has brain metastasis or is resistant to first-line osimertinib. It has been shown to have tumor regression efficacy in models of osimertinib-resistant EGFR C797S mutations. It also has a long residence time in cancer cells and a unique scaffold that does not pose a risk of hyperglycemia through IR/IGF1R inhibition. VRN110755 has kinase selectivity and potent catalytic inhibition potency.<br /><br />There are still unmet medical needs in the treatment of EGFR mutant NSCLC. Osimertinib is recommended as first-line therapy, but there is no approved drug yet for the acquired resistant EGFR mutation C797S. Additionally, patients with brain metastases and intrinsic or acquired osimertinib-resistant EGFR mutations have limited treatment options. Afatinib, which is approved for uncommon EGFR mutations, has poor tolerability.<br /><br />VRN110755 has shown higher cellular potency against EGFR mutants compared to wild-type EGFR. In in vitro and in vivo studies, it has demonstrated anti-tumor efficacy against common, uncommon, and resistance mutations. It has shown superior efficacy to osimertinib in an intracranial brain metastasis model.<br /><br />A first-in-human study of VRN110755 is planned to be initiated in 2023. The drug has a good brain penetrant PK profile and is expected to have target occupancy at low doses. Dose escalation will be performed to explore the maximum tolerated dose. Different clinical cohorts are anticipated to show favorable efficacy based on the specific EGFR mutation types.<br /><br />Overall, VRN110755 shows promise as a potential treatment option for EGFR mutation-driven NSCLC patients with brain metastasis or first-line osimertinib-resistant EGFR mutations. Further studies are needed to assess its safety and efficacy in humans.

Asset Subtitle

Sunghwan Kim

Meta Tag

Speaker Sunghwan Kim

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

VRN110755

therapeutic option

non-small cell lung cancer

NSCLC

EGFR mutations

brain metastasis

osimertinib resistance

tumor regression efficacy

EGFR C797S mutations

kinase selectivity