P2.10-01 ALKTERNATE: A Pilot Study Alternating Lorlatinib with Crizotinib in Patients with ALK+ NSCLC and ALK-inhibitor Resistance

Despite unprecedented survival gains in ALK-gene-rearranged NSCLC, drug resistance remains inevitable, either via ‘ALK-dependent’ on-target mutations, and/or ‘ALK-independent’ bypass tract activation. MET-dysregulation or compound ALK mutations occur commonly in later line ALK-inhibitor(i) therapy, particularly lorlatinib. The first-generation ALKi crizotinib, is an active METi. ALKTERNATE hypothesized that alternating ALKi therapy may alter clonal selection and suppress the manifestation of drug resistance and that ctDNA may detect de novo and acquired resistance mechanisms before they are declared clinically.