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

ALK rearrangements are detected in about 5% of advanced non-small cell lung cancer (NSCLC). Crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib are approved tyrosine kinase inhibitors (TKIs) for ALK-positive NSCLC, but durability of response is partly limited by ALK resistance mutations. The G1202R solvent-front mutation is commonly observed at progression following treatment with crizotinib, ceritinib, alectinib, or brigatinib. Patients with G1202R tumors often respond to lorlatinib but may relapse by acquiring compound mutations such as G1202R/L1196M and G1202R/G1269A.