Lorlatinib

Lorlatinib is a kinase inhibitor with in vitro activity against ALK and ROS1 as well as TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors.

• LORBRENA ® is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. LORBRENA is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.ICD-10: C34.90, C85.90

• LORBRENA is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity [see Warnings and Precautions (5.1) ] . Concomitant use with strong CYP3A inducers.contraindicated

Recommended dosage : 100 mg orally once daily. ( 2.2 ) Severe Hepatic Impairment : 50 mg orally once daily. ( 2.5 , 8.6 , 12.3 ) Renal Impairment : 75 mg orally once daily. ( 2.6 , 8.7 , 12.3 ) 2.1 Patient Selection Select patients for the treatment of metastatic NSCLC with LORBRENA based on the presence of ALK positivity in tumor specimens [see Indications and Usage (1) and Clinical Studies (14) ] . Information on FDA-approved tests for the detection of ALK rearrangements in NSCLC is available at http://www.fda.gov/CompanionDiagnostics . 2.2 Recommended Dosage The recommended dosage of LORBRENA is 100 mg orally once daily, with or without food, until disease progression or unacceptable toxicity [see Clinical Pharmacology (12.3) ] . Swallow tablets whole. Do not chew, crush or split tablets. Do not ingest if tablets are broken, cracked, or otherwise not intact. Take LORBRENA at the same time each day. If a dose is missed, then take the missed dose unless the next dose is due within 4 hours. Do not take 2 doses at the same time to make up for a missed dose. Do not take an additional dose if vomiting occurs after LORBRENA but continue with the next scheduled dose. 2.3 Dosage Modifications for Adverse Reactions The recommended dose reductions are: • First dose reduction: LORBRENA 75 mg orally once daily • Second dose reduction: LORBRENA 50 mg orally once daily Permanently discontinue LORBRENA in patients who are unable to tolerate 50 mg orally once daily. Dosage modifications for adverse reactions of LORBRENA are provided in Table 1.

• Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers : Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA. ( 2.4 , 5.1 ) • Central Nervous System (CNS) Effects : CNS effects include seizures, psychotic effects and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Withhold and resume LORBRENA at same or reduced dose or permanently discontinue LORBRENA based on severity. ( 2.3 , 5.2 ) • Hyperlipidemia : Initiate or increase the dose of lipid-lowering agents. Withhold and resume LORBRENA at same or reduced dose based on severity. ( 2.3 , 5.3 ) • Atrioventricular Block : Withhold and resume LORBRENA at same or reduced dose based on severity. ( 2.3 , 5.4 ) • Interstitial Lung Disease/Pneumonitis : Immediately withhold LORBRENA in patients with suspected ILD/pneumonitis. Permanently discontinue LORBRENA for treatment-related ILD/pneumonitis of any severity. ( 2.3 , 5.5 ) • Hypertension : Monitor blood pressure after 2 weeks and then at least monthly during treatment. For severe hypertension, withhold LORBRENA, then dose reduce or permanently discontinue. ( 2.3 , 5.6 ) • Hyperglycemia : Assess fasting serum glucose prior to starting LORBRENA and regularly during treatment. If not adequately controlled with optimal medical management, withhold LORBRENA, then consider dose reduction or permanently discontinue, based on severity. ( 2.3 , 5.7 ) • Embryo-Fetal Toxicity : Can cause fetal harm.

The following adverse reactions are described elsewhere in the labeling: • Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers [see Warnings and Precautions (5.1) ] • Central Nervous System Effects [see Warnings and Precautions (5.2) ] • Hyperlipidemia [see Warnings and Precautions (5.3) ] • Atrioventricular Block [see Warnings and Precautions (5.4) ] • Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.5) ] • Hypertension [see Warnings and Precautions (5.6) ] • Hyperglycemia [see Warnings and Precautions (5.7) ] Most common (incidence ≥20%) adverse reactions and Grade 3–4 laboratory abnormalities are edema, peripheral neuropathy, weight gain, cognitive effects, fatigue, dyspnea, arthralgia, diarrhea, mood effects, hypercholesterolemia, hypertriglyceridemia, and cough. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or www.pfizer.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the Warnings and Precautions section reflects exposure to LORBRENA in 476 patients who received 100 mg LORBRENA once daily in Study B7461001 (N=327) and Study B7461006 (N=149).

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , LORBRENA can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on LORBRENA use in pregnant women. Administration of lorlatinib to pregnant rats and rabbits by oral gavage during the period of organogenesis resulted in malformations, increased post-implantation loss, and abortion at maternal exposures that were equal to or less than the human exposure at the recommended dose of 100 mg once daily based on AUC (see Data ) . Advise a pregnant woman of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Data Animal Data Preliminary embryo-fetal development studies investigating the administration of lorlatinib during the period of organogenesis were conducted in rats and rabbits. In rabbits, lorlatinib administration resulted in abortion and total loss of pregnancy at doses of 15 mg/kg (approximately 3 times the human exposure at the recommended dose of 100 mg) or greater.

Metabolism

At the recommended dosage, the mean (coefficient of variation [CV] %) maximum plasma concentration (C max ) is 577 ng/mL (42%) and the AUC 0-24h is 5,650 ng·h/mL (39%). Steady-state lorlatinib C max increases proportionally and AUC increased slightly less than proportionally over the dose range of 10 mg to 200 mg orally once daily (0.1 to 2 times the recommended dosage).

• Nov 2, 2018NDANDA210868Pfizer

1. 1Death1,15918%
2. 2Neoplasm Progression6249.6%
3. 3Off Label Use4557.0%
4. 4Weight Increased3565.5%
5. 5Hallucination3525.4%
6. 6Blood Cholesterol Increased3265.0%
7. 7Dyspnoea2523.9%
8. 8Oedema2443.8%
9. 9Fatigue2363.6%
10. 10Oedema Peripheral2323.6%
11. 11Malignant Neoplasm Progression2093.2%
12. 12Peripheral Swelling1963.0%
13. 13Hypercholesterolaemia1762.7%
14. 14Cognitive Disorder1742.7%
15. 15Neuropathy Peripheral1742.7%

The 10 most recently updated of 77 ClinicalTrials.gov registrations naming Lorlatinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma
  Completed · Phase 2 · Interventional · 9 enrolled · University of Milano Bicocca
  NCT03505554updated 2026-06-10
• Vortioxetine for Cognitive Function in ALK-positive NSCLC Treated With Lorlatinib
  Recruiting · Observational · 24 enrolled · Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo
  NCT07633626updated 2026-06-08
• PF-07284892 in Participants With Advanced Solid Tumors
  Terminated · Phase 1 · Interventional · 53 enrolled · Pfizer
  NCT04800822updated 2026-06-04
• AQUA07 in Patients With ALK-Positive Non-Small Cell Lung Cancer
  Not yet recruiting · Phase 1 · Interventional · 102 enrolled · Chugai Pharmaceutical
  NCT07617337updated 2026-06-01
• A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
  Recruiting · Phase 1 · Phase 2 · Interventional · 840 enrolled · Nuvalent Inc.
  NCT05384626updated 2026-05-27
• A Study to Learn About Study Medicine Lorlatinib, as a First-line Treatment in Chinese Adults With ALK-positive a/mNSCLC
  Active not recruiting · Observational · 50 enrolled · Pfizer
  NCT07556549updated 2026-05-22
• A Study of Lorlatinib in Subjects With ROS1-Positive Non-Small Cell Lung Cancer
  Active not recruiting · Phase 2 · Interventional · 70 enrolled · CStone Pharmaceuticals
  NCT05297890updated 2026-05-19
• A Study to Learn About Patients With Non-Small Cell Lung Cancer (NSCLC) Who Took Lorlatinib as Their First Treatment
  Active not recruiting · Observational · 200 enrolled · Pfizer
  NCT07567352updated 2026-05-12
• A Phase 1/2 Study of TRI-611 in ALK-Positive NSCLC
  Recruiting · Phase 1 · Phase 2 · Interventional · 160 enrolled · TRIANA Biomedicines, Inc.
  NCT07491497updated 2026-05-07
• Analysis of the Effectiveness and Safety of Lorlatinib in Untreated ALK-Positive NSCLC Patients in a French Real-World Context
  Recruiting · Interventional · 90 enrolled · Pfizer
  NCT06487078updated 2026-05-06

Frequently asked questions

How does Lorlatinib work?

Lorlatinib is a kinase inhibitor with in vitro activity against ALK and ROS1 as well as TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors.

What is Lorlatinib used for?

According to FDA labeling, Lorlatinib carries indications including: LORBRENA ® is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. LORBRENA is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Lorlatinib?

Lorlatinib is classified as Anaplastic lymphoma kinase (ALK) inhibitors, Kinase Inhibitor, Breast Cancer Resistance Protein Inhibitors, Cytochrome P450 2B6 Inducers, Cytochrome P450 3A Inducers, Cytochrome P450 3A4 Inducers, Kinase Inhibitors, Multidrug and Toxin Extrusion Transporter 1 Inhibitors, Organic Anion Transporter 3 Inhibitors, Organic Cation Transporter 1 Inhibitors, P-Glycoprotein Inducers, Receptor Tyrosine Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Lorlatinib?

Lorlatinib is marketed under brand names including Lorbrena.

What are the contraindications for Lorlatinib?

Lorlatinib labeling lists contraindications including: LORBRENA is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity [see Warnings and Precautions (5.1) ] . Concomitant use with strong CYP3A inducers.. Always consult the full prescribing information and a clinician.