LORVIQUA is a 3rd-generation ALK TKI designed to address unmet medical needs1-4
  • LORVIQUA is a novel, third-generation ALK TKI that has been designed to address two major unmet needs in the treatment of advanced or metastatic ALK+ NSCLC1-3
    • CNS metastases
    • ALK resistance mutations
  • It is the first ALK TKI designed with a macrocyclic ring structure, which provides the ability to effectively cross the blood-brain barrier where it is retained at therapeutic levels2-6
  • LORVIQUA has shown in vitro and clinical activity against ALK resistance mutations, such as the hard-to-treat G1202R mutation, the most common secondary ALK mutation identified in patients prescribed second-generation ALK inhibitors1,6-8

The macrocyclic ring structure of LORVIQUA2

ALK=anaplastic lymphoma kinase; CNS=central nervous system; NSCLC=non-small cell lung cancer; TKl=tyrosine kinase inhibitor.ReferencesReferences:Shaw AT, Solomon BJ, Besse B, et al. ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer. J Clin Oncol. 2019;37(16):1370-1379.Johnson TW, Richardson PF, Bailey S, et al. Discovery of (10R)-7- amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J Med Chem. 2014;57(11):4720-4744. Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with ALK-positive non-small­-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018;19(12):1654-1667. Bauer TM, Shaw AT, Johnson ML, et al. Brain penetration of lorlatinib: cumulative incidences of CNS and non-CNS progression with lorlatinib in patients with previously treated ALK-positive non-small-cell lung cancer. Target Oncol. 2020;15(1):55-65.Shaw AT, Felip E, Bauer TM, et al. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017;18:1590-1599.Hochmair MJ, Fabikan H, Illini O, et al. Later-line treatment with lorlatinib in ALK- and ROS1-rearrangement-positive NSCLC: a retrospective, multicenter analysis. Pharmaceuticals. 2020;13(11):371.Shaw AT, Bauer TM, de Marinis F, et al; CROWN Trial Investigators. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med. 2020;383(21):2018-2029.Gainor JF, Dardaei L, Yoda S, et al. Molecular mechanisms of resistance to first- and second­-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov. 2016;6(10):1118-1133. 
LORVIQUA efficacy
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