ALK fusion + ALK G1202R

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...Ascites mononuclear cells were isolated by Ficoll centrifugation and cultured in media (DMEM F12 Glutamax, 10% antibiotics/antimycotics, 10% FBS, hydrocortisone, adenine, RockInhibitor, and 1/10 cholera toxin)... NVL-655 has demonstrated activity in many preclinical models bearing ALK compound mutations, including the MR448re (EML4-ALK v3 G1202R/T1151M) model. The potent preclinical activity of NVL-655 suggests potential clinical utility for ALK-positive patients, including those with resistant compound mutations. The MR448re PDC and xenograft are valuable additions to the ALK therapeutic research landscape where there is limited availability of patient-derived models with lorlatinib-resistant ALK compound mutations.