Lazertinib, a third generation kinase inhibitor of epidermal growth factor receptor ( EGFR ), is an antineoplastic agent.1, 2
Lazertinib is used in combination with amivantamab for the first-line treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.1, 6 Information on FDA-approved companion diagnostic tests for the detection of EGFR mutations in NSCLC is available at [Web].1
The efficacy of lazertinib (in combination with amivantamab) for treatment of NSCLC was established in the MARIPOSA trial, a randomized, active-controlled, multicenter study.1, 2, 3 A total of 1,074 patients with untreated locally advanced or metastatic NSCLC with either exon 19 deletions or exon 21 L858R substitution EGFR mutations were randomized; 429 patients were assigned to an open-label combination of lazertinib and amivantamab, while 429 patients received osimertinib monotherapy and 216 patients received lazertinib monotherapy, both in a double-blind manner.1, 2, 3 Lazertinib was administered at a dosage of 240 mg orally once daily, combined with IV amivantamab administered at a dose of 1,050 mg for patients <80 kg or 1,400 mg for patients ≥80 kg once weekly for 4 weeks, then every 2 weeks starting at week 5.1, 2, 3 The comparison groups received either osimertinib 80 mg or lazertinib 240 mg taken orally once daily.1, 2, 3 The median patient age was 64 years (range: 25 to 88); 58% of patients were Asian, 38% were white, 61% were female, 70% had no smoking history, 60% had no history of brain metastases, 89% were in initial Stage IV at diagnosis, and 66% had an Eastern Cooperative Oncology Group (ECOG) score of 1.1, 2 Mutations included exon 19 deletion (60%) and exon 21 L858R substitution (40%).2
The primary endpoint, progression-free survival (PFS) as assessed by blinded independent central review, was analyzed between the amivantamab-lazertinib combination and osimertinib groups, with the lazertinib monotherapy group included to evaluate the individual contributions of each agent in the combination therapy.1, 2, 3 The results showed a statistically significant improvement in PFS with the amivantamab-lazertinib combination compared with osimertinib; median PFS was 23.7 months in the amivantamab-lazertinib group compared with 16.6 months in the osimertinib group.1, 2 Among patients who achieved a confirmed response (complete or partial tumor regression according to the RECIST [Response Evaluation Criteria in Solid Tumors] criteria version 1.1), the overall response rate was 78% in the amivantamab-lazertinib combination group and 73% in the osimertinib group.1, 2 The median duration of response was 25.8 months for the combination group compared to 16.7 months for the osimertinib group.1, 2 The median PFS for the lazertinib monotherapy group was 18.5 months, which did not differ from the osimertinib group.2, 4 Deaths did not differ between groups with 97 in the amivantamab-lazertinib combination and 117 in the osimertinib group.2
EGFR -activating mutations are present in approximately 30% of NSCLC cases and observed at a higher rate in Asian compared with Western populations, in nonsmokers compared with smokers, and in patients with adenocarcinoma histology.5, 27, 29 The American Society of Clinical Oncology (ASCO) has published guidelines for the management of stage IV NSCLC with driver alterations including EGFR mutations.6 The guidelines strongly recommend osimertinib with platinum-pemetrexed chemotherapy or lazertinib plus amivantamab as first-line treatment options for patients with EGFR exon 19 deletions or exon 21 L858R substitution mutations.6
Lazertinib is administered orally with or without food.1 The tablets should be swallowed whole and should not be cut, crushed, or chewed.1
Store the tablets at 20-25°C; excursions between 15-30°C are permitted.1
The recommended adult dosage of lazertinib for the treatment of advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations is 240 mg once daily, in combination with amivantamab.1 Continue treatment until disease progression or unacceptable toxicity.1 Administer lazertinib any time prior to amivantamab when given on the same day.1
If a dose of lazertinib is missed within 12 hours, the patient should be instructed to take the missed dose.1 If more than 12 hours has passed since the dose was to be given, the patient should be instructed to take the next dose at its scheduled time.1
Refer to the amivantamab prescribing information for recommended amivantamab dosing information.1
Dosage Modification for Toxicity
If an adverse reaction occurs, treatment interruption, dosage reduction, and/or discontinuation of therapy may be necessary based on severity of the adverse event.1
The manufacturer's recommended dosage reduction schedule and dosing modifications for adverse reactions are provided in Tables 1 and 2.1
Refer to the amivantamab prescribing information for recommended amivantamab dosage modification.1
Dose | Lazertinib Dose Level |
|---|---|
Starting dose | 240 mg once daily (one 240-mg tablet) |
1st dose reduction | 160 mg once daily (two 80-mg tablets) |
2nd dose reduction | 80 mg once daily (one 80-mg tablet) |
3rd dose reduction | Discontinue lazertinib |
Adverse Reaction | Severity, Dosage Modification |
|---|---|
Venous thromboembolic events (VTE) | Grade 2 or 3: Withhold lazertinib and amivantamab. Administer anticoagulant treatment as clinically indicated. Once anticoagulant treatment has been initiated, resume lazertinib and amivantamab at the same dose level, at the discretion of the healthcare provider. Grade 4 or recurrent Grade 2 or 3 (despite therapeutic level anticoagulation): Withhold lazertinib and permanently discontinue amivantamab. Administer anticoagulant treatment as clinically indicated. Once anticoagulant treatment has been initiated, treatment can continue with lazertinib at the same dose level, at the discretion of the healthcare provider. |
Interstitial lung disease (ILD)/Pneumonitis | Any Grade: Withhold lazertinib and amivantamab if ILD/pneumonitis is suspected and permanently discontinue if ILD/pneumonitis is confirmed. |
Dermatologic adverse reactions (including dermatitis acneiform, pruritus, dry skin) | Grade 1: Initiate supportive care management as clinically indicated. Grade 2: Initiate supportive care management as clinically indicated. If there is no improvement after 2 weeks, reduce amivantamab dose and continue lazertinib at the same dose. Reassess every 2 weeks, if no improvement, reduce lazertinib dose until ≤Grade 1 (Table 1), then may resume previous dose of lazertinib at the discretion of the healthcare provider. Grade 3: Withhold lazertinib and amivantamab. Initiate supportive care management as clinically indicated. Upon recovery to ≤Grade 2, resume lazertinib at the same dose or consider dose reduction, resume amivantamab at a reduced dose. If there is no improvement within 2 weeks, permanently discontinue both lazertinib and amivantamab. Grade 4 (including severe bullous, blistering or exfoliating skin conditions): Initiate supportive care management as clinically indicated. Permanently discontinue amivantamab. Withhold lazertinib until recovery ≤Grade 2 or baseline. Upon recovery to ≤Grade 2, resume lazertinib at a reduced dose at the discretion of the healthcare provider. |
Hepatotoxicity | Grade 3-4: Withhold lazertinib and amivantamab until the adverse reaction resolves to ≤Grade 1 or baseline. Resume both drugs at a reduced dose or lazertinib alone. Consider permanently discontinuing both lazertinib and amivantamab if recovery does not occur within 4 weeks. |
Other adverse reactions | Grade 3-4: Withhold lazertinib and amivantamab until the adverse reaction resolves to ≤Grade 1 or baseline. Resume both drugs at a reduced dose or lazertinib alone. Consider permanently discontinuing both lazertinib and amivantamab if recovery does not occur within 4 weeks. |
No dose adjustment is recommended in patients with mild (total bilirubin ≤upper limit of normal (ULN) and AST > ULN or total bilirubin ≤1.5 times the ULN and any AST) or moderate (total bilirubin ≤1.5 to 3 times the ULN and any AST) hepatic impairment.1
No dose adjustment is recommended for patients with mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-89 mL/min).1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Lazertinib, in combination with amivantamab, can lead to serious and potentially fatal VTE, including DVT and PE, primarily within the first four months of therapy.1 In the MARIPOSA study, 36% of patients receiving lazertinib with amivantamab experienced VTE, with Grade 3 events in 10% and Grade 4 in 0.5%.1, 2 During the study, 5 patients (1.2%) experienced VTE despite anticoagulation.1 There were two fatal VTE cases (0.5%); VTE led to dose interruptions in 7% of patients, dose reductions in 0.5%, and permanent discontinuation in 1.9%.1 The median onset time for VTE was 84 days (range: 6 to 777 days).1
Administer prophylactic anticoagulation for the first 4 months of treatment with lazertinib and amivantamab; use of vitamin K antagonists is not recommended.1 Monitor for signs and symptoms of VTE and treat as medically appropriate.1
If VTE occurs, withhold lazertinib and amivantamab therapy based on severity.1 Once anticoagulant treatment has been initiated, resume lazertinib and amivantamab at the same dose level at the discretion of the healthcare provider.1 In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue amivantamab.1 Continue treatment with lazertinib at the same dose level at the discretion of the healthcare provider.1 Refer to the amivantamab prescribing information for recommended amivantamab dosage modification. 1
Interstitial Lung Disease/Pneumonitis
Lazertinib, in combination with amivantamab, may lead to ILD or pneumonitis.1 In the MARIPOSA study, ILD/pneumonitis occurred in 3.1% of patients receiving the combination, with Grade 3 events in 1.0% and Grade 4 in 0.2%.1, 2 There was one fatal ILD/pneumonitis case (0.2%), and 2.9% of patients permanently discontinued lazertinib and amivantamab due to these conditions.1, 2
Monitor patients for new or worsening symptoms suggestive of ILD/pneumonitis, such as dyspnea, cough, and fever.1 Immediately withhold lazertinib and amivantamab if ILD/pneumonitis is suspected, and discontinue permanently if confirmed.1
Dermatologic Adverse Reactions
Lazertinib, in combination with amivantamab, can cause severe dermatologic reactions, including acneiform dermatitis, pruritus, and dry skin.1 In the MARIPOSA study, rash occurred in 86% of patients treated with lazertinib in combination with amivantamab, including Grade 3 rash in 26% of patients.1, 2 The median time to onset of rash was 14 days (range: 1 to 556 days).1, 2 Rash led to dose reductions of lazertinib in 19% of patients, dose interruptions in 30%, and permanent discontinuation of lazertinib in 1.7%.1, 2
At treatment initiation of lazertinib in combination with amivantamab, patients should use appropriate prophylactic and concomitant medications (e.g., oral and/or topical antibiotics), limit sun exposure during and for 2 months post-treatment, and use protective clothing and broad-spectrum UVA/UVB sunscreen to reduce the risk and severity of dermatologic adverse reactions.1
If skin reactions develop, administer supportive care including topical corticosteroids and topical and/or oral antibiotics.1 For Grade 3 reactions, administer oral steroids and consider dermatologic consultation.1 Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist.1 Withhold, reduce the dose, or permanently discontinue lazertinib and amivantamab based on severity.1
Lazertinib in combination with amivantamab can cause severe hepatotoxicity (including increased ALT and AST).1 In the MARIPOSA trial, hepatotoxicity occurred in 49% of lazertinib-treated patients, including Grade 3 events in 9.3% of patients and Grade 4 in 0.5%.1 Interruption of lazertinib therapy for hepatotoxicity occurred in 8% of patients, the dose was reduced in 1.4% and permanently discontinued in 0.2%.1
Clinicians should perform liver function tests (including ALT, AST, and total bilirubin) before initiation of lazertinib and during treatment, as clinically indicated.1 Withhold, reduce the dose, or permanently discontinue lazertinib and amivantamab based on severity.1
Lazertinib, in combination with amivantamab, can cause ocular toxicity, including keratitis.1 In the MARIPOSA trial, ocular toxicity occurred in 16% of patients treated with lazertinib and amivantamab, with Grade 3 or 4 toxicity in 0.7%.1 Promptly refer patients with new or worsening eye symptoms to an ophthalmologist.1
Withhold, reduce the dose, or permanently discontinue amivantamab and continue lazertinib based on severity.1
Based on findings from animal studies and its mechanism of action, lazertinib can cause fetal harm when administered to a pregnant woman.1 In animal reproduction studies, oral administration of lazertinib to pregnant animals during the period of organogenesis resulted in reduced embryo-fetal survival and fetal body weight in rats and malformations in rabbits at exposures approximately 4 and 0.5 times, respectively, the human exposure at the recommended dose of 240 mg/day.1
Advise pregnant women and females of reproductive potential of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with lazertinib and for 3 weeks after the last dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment with lazertinib and for 3 weeks after the last dose.1
Although there are no available data in pregnant women, animal studies suggest that lazertinib may cause fetal harm.1 Oral administration of lazertinib to pregnant animals during the period of organogenesis resulted in reduced embryo-fetal survival and fetal body weight in rats and malformations in rabbits at exposures approximately 4 and 0.5 times, respectively, the human exposure at the recommended dose of 240 mg/day.1 Advise pregnant women of the potential risk to a fetus.1
There are no data on the presence of lazertinib or its metabolites in human milk or their effects on the breastfed child or on milk production.1 Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with lazertinib and for 3 weeks after the last dose.1 Refer to the amivantamab prescribing information for lactation information during treatment with amivantamab.1
Females and Males of Reproductive Potential
Based on animal data and its mechanism of action, lazertinib can cause fetal harm when administered to a pregnant woman.1
Verify the pregnancy status of females of reproductive potential prior to initiating lazertinib.1
Advise females of reproductive potential to use effective contraception during treatment with lazertinib and for 3 weeks after the last dose.1 Refer to the amivantamab prescribing information for recommended duration of contraception during treatment with amivantamab.1
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with lazertinib and for 3 weeks after the last dose.1
Based on findings in animals, lazertinib may impair fertility in females and males of reproductive potential.1 The effects on female fertility were reversible.1 The effects on male testes in animal studies were not reversible within a 2-week recovery period. 1
The safety and effectiveness of lazertinib in pediatric patients have not been established.1
Of the 421 patients with locally advanced or metastatic NSCLC treated with lazertinib in combination with amivantamab in the MARIPOSA study, 45% were 65 years of age and older and 12% were 75 years of age and older.1 No overall differences in safety or effectiveness were observed between patients 65 years of age and older and younger patients.1
No dose adjustment is recommended in patients with mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin ≤1.5 times ULN and any AST) or moderate (total bilirubin ≤1.5 to 3 times ULN and any AST) hepatic impairment.1
Lazertinib has not been studied in patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).1
No dose adjustment is recommended in patients with mild or moderate renal impairment (eGFR 30-89 mL/min).1
Lazertinib has not been studied in patients with severe renal impairment or end-stage renal disease (eGFR <30 mL/min).1
The most common adverse reactions (≥20%) of lazertinib in combination with amivantamab were rash, nail toxicity, infusion-related reaction (amivantamab), musculoskeletal pain, edema, stomatitis, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, and nausea.1
The most common Grade 3 or 4 laboratory abnormalities (≥2%) of lazertinib in combination with amivantamab were decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, increased GGT, and increased magnesium.1
Lazertinib is a cytochrome P-450 (CYP) 3A4 substrate.1 The drug inhibits CYP3A4, UDP-glucuronosyltransferase 1A1 (UGT1A1), breast cancer resistance protein (BCRP), and organic cation transporter 1 (OCT1).1 Lazertinib does not induce CYP1A2, CYP2B6, or CYP3A4.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Because lazertinib is a CYP3A4 substate, avoid concomitant use of the drug with strong or moderate CYP3A4 inducers.1 Consider alternative medications that do not induce CYP3A4.1
Lazertinib is a weak CYP3A4 inhibitor and can increase the concentrations of CYP3A4 substrates when used concurrently.1
Concomitant use of rifampin, a strong CYP3A4 inducer, decreased the peak concentration and AUC of lazertinib by 72% and 83%, respectively.1
Concomitant use of efavirenz, a moderate CYP3A4 inducer, is predicted to decrease the peak concentration and AUC of lazertinib by 32% and 44%, respectively.1
Concomitant use of itraconazole, a strong CYP3A4 inhibitor, increased the peak concentration and AUC of lazertinib by 20% and 50%, respectively.1
Concomitant use of midazolam, a CYP3A4 substrate, increased the peak concentration and AUC of midazolam by 40% and 50%, respectively.1
Drugs Affecting or Affected by Transport Systems
Lazertinib is a BCRP inhibitor and may increase concentrations of BCRP substrates when used concomitantly.1 Monitor for adverse reactions associated with a BCRP substrate when minimal concentration changes could lead to serious adverse reactions.1
Concomitant use with rosuvastatin, a BCRP substrate, increased the peak concentration and AUC of rosuvastatin by 120% and 100%, respectively.1
No clinically significant pharmacokinetic differences were observed or predicted with concomitant use of lazertinib and metformin (OCT1 substrate) or raltegravir (UGT1A1 substrate).1
Lazertinib exposure remained unchanged when administered with gastric acid reducing drugs.1
Lazertinib is a third generation kinase inhibitor of EGFR that inhibits EGFR exon 19 deletions and exon 21 L858R substitution mutations at lower concentrations than wild-type EGFR .1, 2 In human non-small cell lung cancer (NSCLC) cells and mouse xenograft models of EGFR exon 19 deletions or exon 21 L858R substitution mutations, lazertinib demonstrated anti-tumor activity.1 In a mouse xenograft model of human NSCLC with an EGFR L858R mutation, the combination of lazertinib and amivantamab demonstrated greater in vivo anti-tumor activity compared to treatment with either agent alone.1
Lazertinib pharmacokinetics indicate dose-proportional increases in drug exposure from 20 mg to 320 mg with steady-state levels reached by day 15.1 Lazertinib is absorbed within 2-4 hours with a half-life of 3.7 days.1 Elimination is primarily through glutathione conjugation (enzymatic or non-enzymatic) with cytochrome P-450 (CYP) 3A4 as a minor pathway.1 Excretion occurs mainly via feces (86%) with minimal unchanged drug in urine (<0.2%).1 Patients with at least one glutathione S-transferase mu 1 ( GSTM1 ) normal function allele exhibit 44% lower lazertinib serum levels than those with two no-function alleles, though no clinically significant safety or efficacy differences have been observed based on GSTM1 genotype when used with amivantamab.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Lazertinib can be obtained through specialty pharmacy distributors. For additional information, consult the manufacturer's website at [Web].
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 80 mg (of lazertinib) | Lazcluze® | Janssen Biotech |
240 mg (of lazertinib) | Lazcluze® | Janssen Biotech |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions August 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Janssen Biotech, Inc. LAZCLUZE® (lazertinib) ORAL prescribing information. 2026 Apr. [Web]
2. Cho BC, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med . 2024;391(16):1486-1498.
3. Cho BC, Felip E, Hayashi H, et al. MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. Future Oncol . 2022;18(6):639-647.
4. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 219008Orig1s000: Multidisciplinary Review. From FDA website.
5. Zhang YL, Yuan JQ, Wang KF, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget . 2016;7(48):78985-78993.
6. Puri S, Ismaila N, Azar IH, et al. Therapy for stage IV non-small cell lung cancer with driver alterations: ASCO living guideline, Version 2026.3.2. J Clin Oncol . Published online May 28, 2026.
7. Felip E, Cho BC, Gutiérrez V, et al. Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA. Ann Oncol . 2024;35(9):805-816.
27. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res . 2015 Aug 15;5(9):2892-911. PMID: 26609494; PMCID: PMC4633915.
29. Jotte RM, Spigel DR. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance. Cancer Med . 2015 Nov;4(11):1621-32. Epub 2015 Aug 26. PMID: 26310719; PMCID: PMC4673988.