2022 World Conference on Lung Cancer (ePosters)-EP08.02-020. Preclinical Activity of NVL-655 in a Patient-Derived NSCLC Model with Lorlatinib-Resistant ALK G1202R/T1151M Mutation

EP08.02-020. Preclinical Activity of NVL-655 in a Patient-Derived NSCLC Model with Lorlatinib-Resistant ALK G1202R/T1151M Mutation

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NVL-655 is a novel ALK inhibitor that has shown potent activity against various forms of ALK-positive cancers, regardless of fusion partner, activating mutation, or resistance mutation. Compared to other ALK inhibitors, NVL-655 has a broader range of activity and selectively targets ALK while sparing TRKB. It has demonstrated efficacy in NSCLC models with resistance mutations and has shown promising activity in ALK-positive cholangiocarcinoma models. NVL-655 offers a potential therapeutic option for ALK-positive cancers, including those in the central nervous system.<br /><br />The selectivity of NVL-655 in inhibiting ALK while sparing TRKB is significant as TRKB is associated with adverse events and toxicities. This selectivity makes NVL-655 a promising candidate for treating ALK-positive cancers in the central nervous system.<br /><br />In preclinical studies, NVL-655 exhibited higher selectivity for ALK and showed efficacy in models with resistance mutations. It demonstrated potent activity and selectivity against ALK in various ALK cancer models, offering a potential treatment option for ALK-positive cancers, including those with resistance mutations.<br /><br />Further research and clinical trials are needed to validate these findings and evaluate the safety and efficacy of NVL-655 in ALK-positive cancers. However, based on the preclinical characterization and in vivo studies, NVL-655 shows promise as a treatment option for ALK-positive cancers that have progressed on earlier-generation ALK inhibitors. It is currently being evaluated in a Phase 1/2 clinical trial for advanced NSCLC and other solid tumors with ALK rearrangement or activating ALK mutations.<br /><br />In summary, NVL-655 is a novel ALK inhibitor that has demonstrated potent activity and selectivity against ALK in various ALK cancer models. It offers a potential treatment option for ALK-positive cancers, including those with resistance mutations. Further research and clinical trials are needed to confirm its safety and efficacy.

Asset Subtitle

Anupong Tangpeerachaikul

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Speaker Anupong Tangpeerachaikul

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

NVL-655

ALK inhibitor

ALK-positive cancers

fusion partner

activating mutation

resistance mutation

NSCLC models

cholangiocarcinoma models

selectivity

central nervous system