2023 World Conference on Lung Cancer (Posters)-P1.02. Identifying Biomarkers of Response to Ensartinib, Lorlatinib, and Alectinib in an ALK+ Non-Small Cell Lung Cancer Preclinical Model (ResCu)

P1.02. Identifying Biomarkers of Response to Ensartinib, Lorlatinib, and Alectinib in an ALK+ Non-Small Cell Lung Cancer Preclinical Model (ResCu) - PDF(Slides)

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ResistanceBio has developed a novel method and algorithm called ResCu that can identify resistance mechanisms that are not detectable using current technologies. They use a proprietary tissue culture system called the ResCu system to accurately replicate the emergence of resistance observed in clinical settings. This system allows them to capture the emergence of resistant subpopulations and their frequency of occurrence at clinically relevant doses. It can be used with both small molecule inhibitors and biologics. <br /><br />The ResCu system creates a microenvironment similar to human tissue, maintaining a similar pH under fluid exchange, which allows for resistance to occur under clinical conditions. This enables ResistanceBio to identify the strengths and vulnerabilities of a compound and develop precision medicine strategies and drug combinations based on the natural adaptations of cancer cells.<br /><br />The document discusses the specific case of ALK NSCLC (non-small cell lung cancer) and the current shift in using lorlatinib and alectinib as first-line therapies. While these therapies are effective, their potential to generate drug resistance has not been fully characterized. The ResCu system can detect known resistance mechanisms and identify potential synergies and novel mechanisms.<br /><br />Ensartinib is highlighted as a promising therapy that has shown to suppress resistance mutations and double median PFS (progression-free survival) in ALK NSCLC. The ResCu system can determine if ensartinib is more effective as a first-line therapy compared to lorlatinib and alectinib.<br /><br />The document also discusses the evolution of ALK inhibitor (ALKi) resistance using the ResCu system. It demonstrates that the genetic background has an impact on the durability of response to ALKi. The ResCu system has been validated against known clinical resistance mechanisms, and biomarkers of specific ALKi response have been identified in clinical samples.<br /><br />In conclusion, ResistanceBio's ResCu system is a promising tool for identifying resistance mechanisms and developing precision medicine strategies in cancer treatment. It can accurately replicate resistance observed in clinical settings and has the potential to improve the effectiveness of ALK NSCLC therapies.

Asset Subtitle

Christopher Bulow

Meta Tag

Speaker Christopher Bulow

Topic Tumor Biology: Preclinical Biology - Molecular Therapeutic Targets

Keywords

ResistanceBio

ResCu

resistance mechanisms

clinically relevant doses

precision medicine strategies

drug combinations

ALK NSCLC

lorlatinib

alectinib

ensartinib