LORVIQUA® (lorlatinib) as monotherapy is indicated for the treatment of patients with ALK+ metastatic NSCLC whose disease has progressed on alectinib or ceritinib as the first ALK TKI therapy, or crizotinib and at least one other ALK TKI therapy1
Molecular Structure
LORVIQUA®: A potent third-generation ALK TKI designed to address unmet  medical needs2-4
  • LORVIQUA ® is the first ALK TKI with a  macrocyclic ring designed to address the  unmet needs in ALK+ advanced NSCLC2-4
  • LORVIQUA ®  effectively crosses the blood-brain  barrier and is retained at therapeutic levels4-6*
  • LORVIQUA ®  has shown in vitro and clinical  activity against ALK resistance mutations, such  as the hard-to-treat G1202R mutation7,8


The novel macrocyclic ring structure of LORVIQUA®2
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*Mean CSF concentrations    are  shown to correspond to up to 75% of unbound plasma concentrations5,6


For Healthcare Professionals only​​​​​​​

Abbreviations: ALK+, Anaplastic lymphoma kinase positive; CSF, cerebrospinal fluid; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase


References
1. Pfizer. LORVIQUA® (lorlatinib) Prescribing Information, Available from:  http://labeling.pfizer.com/ShowLabeling.aspx?id=12540 Accessed September 23,2021.
2. Johnson TW,  Richardson P F, 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.
3. Johnson TW.  Structural  data in the discovery of lorlatinib and   insights   into mechanisms of ALK acquired resistance.  Oral presentation at American Association for Cancer Research (AACR); 14-18 April 2018; Chicago, IL, USA.
4. Solomon  Bl, Besse B, Bauer TM, et al.  Lorlatinlb  in  patients with  ALK-positive  non-small-cell lung cancer: results  from a global phase 2 study. Lancet Oncol. 2018;19(12):1654-1667.
5. 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
6. 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 phase1 trial. Lancet  Oncol . 2017;18(12):1590-1599.
7. 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 Discov2016:6(10):1118-1133.
8. Shaw AT, Solomon  BI, 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.



The use of lorlatinib has been associated with increases in serum cholesterol and triglycerides. Serum cholesterol and triglycerides should be monitored before the initiation of lorlatinib; 2, 4, and 8 weeks after initiating lorlatinib, and periodically thereafter. Initiation, or increase in the dose, of lipid-lowering agents is required.
Central nervous system (CNS) effects have been observed in patients receiving lorlatinib including seizures, psychotic effects, changes in cognitive function, mood (including suicidal ideation), mental status, sleep, and speech. Dose modification or discontinuation may be required for those patients who develop CNS effects.
PR interval prolongation and atrioventricular (AV) block events have been reported in patients receiving lorlatinib. Monitor electrocardiogram (ECG) prior to initiating lorlatinib and monthly thereafter, particularly in patients with predisposing conditions to the occurrence of clinically significant cardiac events. Dose modification may be required for those patients who develop AV block.
Elevations of lipase and/or amylase have occurred in patients receiving lorlatinib. Median time of occurrence of increase in serum lipase and amylase is 70 days (range: 7 days to 696 days) and 41 days (range: 7 days to 489 days), respectively. Risk of pancreatitis should be considered in patients receiving lorlatinib due to concomitant hypertriglyceridemia and/or a potential intrinsic mechanism. Patients should be monitored for lipase and amylase elevations prior to the start of lorlatinib treatment and regularly thereafter as clinically indicated.
Severe or life threatening pulmonary adverse drug reactions consistent with ILD/pneumonitis have occurred with lorlatinib. Any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough and fever) should be promptly evaluated for ILD/pneumonitis. Lorlatinib should be withheld and/or permanently discontinued based on severity.
Hypertension has been reported in patients receiving lorlatinib. Blood pressure should be controlled prior to the initiation of lorlatinib. Blood pressure should be monitored after 2 weeks and at least monthly thereafter during treatment with lorlatinib. Lorlatinib should be withheld and resumed at a reduced dose or permanently discontinued based on severity.
Hyperglycemia has occurred in patients receiving lorlatinib. Fasting serum glucose should be assessed prior to the initiation of lorlatinib and monitored periodically thereafter. Lorlatinib should be withheld and resumed at a reduced dose or permanently discontinued based on severity.
Concomitant use of any strong CYP3A inducer is contraindicated. Any strong CYP3A inducers have to be discontinued for at least 3 plasma half-lives of the strong CYP3A inducer before lorlatinib treatment is started. No clinically meaningful changes in liver function tests were seen in healthy subjects after receiving a combination of lorlatinib with the moderate CYP3A inducer modafinil.
Women of childbearing potential should be advised to avoid getting pregnant while receiving lorlatinib. Male fertility may be compromised during treatment with lorlatinib. Men should seek advice on effective fertility preservation before treatment.
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​​​​​​​LORVIQUA® Efficacy

​​​​​​​LORVIQUA
® Safety Profile
LORVIQUA® Dosing and Therapy
​​​​​​​Management
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