2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.03F.01 Modeling the Relationship of Clinical Safety Profile of EGFR Inhibitors with Wild-Type EGFR Inhibition in Cellular Model

EP.03F.01 Modeling the Relationship of Clinical Safety Profile of EGFR Inhibitors with Wild-Type EGFR Inhibition in Cellular Model

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This document outlines a study by BlossomHill Therapeutics investigating the relationship between the clinical safety profile of Epidermal Growth Factor Receptor (EGFR) inhibitors and their inhibitory activity on wild-type EGFR, using a cellular model. The study focuses on two common adverse events (AEs) associated with EGFR inhibitors: rash and diarrhea.<br /><br />The research utilizes A431 cell proliferation assays to determine the half-maximal inhibitory concentration (IC50) of various EGFR inhibitors such as gefitinib, afatinib, osimertinib, and others. The results reveal strong correlations between the IC50 values and the incidence and severity of rash and diarrhea, particularly at Grade 3 levels. Statistical analyses using Pearson correlation and regression models confirm these findings, underscoring a significant and quantifiable relationship between the preclinical cellular activity of EGFR inhibitors and their clinical safety profile.<br /><br />The study provides insight into the nonclinical development of EGFR inhibitors by predicting potential clinical safety outcomes based on in vitro data. This approach could enable better safety assessments at early stages of drug development, helping to understand the safety profiles of new therapies targeting EGFR.<br /><br />Despite the promising results, the study acknowledges limitations related to data scope and the precision of statistical models, suggesting that further research could refine these models by incorporating more granular data and variability estimates.<br /><br />In conclusion, the robust quantitative relationships established in this study between preclinical cellular activities and clinical AE outcomes can significantly inform the development and safety evaluation of EGFR inhibitors, potentially improving the therapeutic strategies for non-small cell lung cancer and other conditions targeted by these inhibitors.

Asset Subtitle

Jihao Zhou

Meta Tag

Speaker Jihao Zhou

Topic Tumor Biology – Translational Biology

Keywords

BlossomHill Therapeutics

EGFR inhibitors

clinical safety profile

A431 cell proliferation

IC50 values

rash and diarrhea

Pearson correlation

nonclinical development

drug safety assessment

therapeutic strategies