^
    over4years
    Diverse resistance mechanisms to the third-generation ALK inhibitor lorlatinib in ALK-rearranged lung cancer. (PubMed, Clin Cancer Res)
    This study shows that mechanisms of resistance to lorlatinib are diverse and complex, requiring new therapeutic strategies to tailor treatment upon disease progression.
    Journal
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK rearrangement • ALK mutation • ALK G1202R • ALK C1156Y • ALK G1269A • ALK L1196M • ALK C1156Y + ALK G1202R • ALK L1196M + ALK G1202R
    |
    Lorbrena (lorlatinib)
    over4years
    [VIRTUAL] The value of detecting resistance through liquid biopsy (ESMO 2020)
    Table: 1195P * ALK fusion+ pts received prior alectinib (median 3 prior TKI); EGFR T790M+ pts received prior osimertinib (median 2 prior TKI).**concurrent aberrations (G1202R+C1156Y; MET amp+ T790M; FGFR1 amp + CDK4 amp; C797S + BRAF; EGFR amp+CCND2 amp) Legal entity responsible for the study: The authors. Funding: Princess Margaret Cancer Foundation; Guardant Health. Clinical trial identification: NCT03576937.
    Liquid biopsy
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FGFR1 (Fibroblast growth factor receptor 1) • CDK4 (Cyclin-dependent kinase 4) • CCND2 (Cyclin D2)
    |
    EGFR T790M • ALK fusion • EGFR C797S • ALK G1202R • ALK C1156Y • EGFR T790M + EGFR C797S • FGFR1 fusion • ALK C1156Y + ALK G1202R
    |
    Tagrisso (osimertinib) • Alecensa (alectinib)
    over4years
    [VIRTUAL] Longitudinal circulating tumor DNA (ctDNA) analysis predicts response and reveals the resistance mechanisms of ensartinib in ALK+ NSCLC patients (pts) progressed on crizotinib: Updated analysis of a phase II clinical trial (AACR-II 2020)
    Consistent with previous reports, ensartinib showed high clinical efficacy. Longitudinal ctDNA analysis could be a powerful tool in predicting treatment outcomes and revealing resistant mechanisms of ensartinib. We observed G1269A, G1202R and E1210K as the major resistant mutations to ensartinib.
    Clinical • P2 data
    |
    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53)
    |
    TP53 mutation • ALK fusion • ALK mutation • ALK G1202R • ALK C1156Y • ALK G1269A • ALK I1171 • ALK E1210K • ALK C1156Y + ALK G1202R
    |
    Xalkori (crizotinib) • Ensacove (ensartinib)