Lazertinib Mesylate (Monograph)

Brand name: Lazcluze
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Feb 10, 2025. Written by ASHP.

Introduction

Antineoplastic agent; a third generation kinase inhibitor of epidermal growth factor receptor (EGFR).

Uses for Lazertinib Mesylate

Non-Small Cell Lung Cancer

In combination with amivantamab for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

Guidelines from the American Society of Clinical Oncology (ASCO) support the use of amivantamab plus lazertinib as a first-line treatment approach in patients with EGFR exon 19 deletions or exon 21 L858R substitution mutations.

Lazertinib Mesylate Dosage and Administration

General

Pretreatment Screening

Select patients for treatment of non-small cell lung cancer (NSCLC) based on presence of EGFRexon 19 deletions or exon 21 L858R substitution mutations in tumor or plasma specimens; if mutations are not detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests available at [Web].
Verify pregnancy status in females of reproductive potential.

Patient Monitoring

Monitor patients for signs and symptoms of VTE, including DVT and PE, especially during the first 4 months of treatment when prophylactic anticoagulation is recommended.
Monitor patients for new or worsening respiratory symptoms, such as shortness of breath, cough, or fever, indicative of interstitial lung disease (ILD)/pneumonitis.
Monitor patients for dermatologic reactions, including rash.
Monitor patients for new or worsening ocular symptoms, such as eye redness, eye pain, or visual disturbances, and refer to an ophthalmologist if necessary.
Monitor for decreased albumin, sodium, potassium, hemoglobin, increased liver enzymes (ALT, AST), and gamma-glutamyl transferase (GGT).

Premedication and Prophylaxis

Prophylactic anticoagulation is recommended for the first 4 months of treatment; the use of a vitamin K antagonist is not recommended. Consider discontinuation of anticoagulant prophylaxis if no VTE signs or symptoms occur during the first 4 months.
Administer alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream and consider prophylactic measures (e.g., oral antibiotics) to reduce the risk of dermatologic reactions. Advise patients to wear protective clothing, use broad spectrum UVA/UVB sunscreen, and limit sun exposure during and for 2 months after treatment.

Administration

Oral Administration

Administer orally with or without food. Swallow tablets whole and do not cut, crush, or chew.

Dosage

Adults

Non-Small Cell Lung Cancer

Oral

Recommended dosage is 240 mg once daily in combination with amivantamab. Continue treatment until disease progression or unacceptable toxicity. Administer lazertinib any time prior to amivantamab when given on the same day.

If a dose is missed within 12 hours, instruct the patient to take the missed dose. If >12 hours has passed since the dose was to be given, instruct the patient to take the next dose at its scheduled time.

Refer to the amivantamab prescribing information for recommended amivantamab dosing information.

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.

The manufacturer's recommended dosage reduction schedule and dosing modifications for adverse reactions are provided in Tables 1 and 2.

Refer to the amivantamab prescribing information for recommended amivantamab dosage modification.

Table 1. Recommended Dosage Reductions for Adverse Reactions1
	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

Table 2. Recommended Management and Dosage Modifications for Adverse Reactions1
Adverse Reaction	Severity, Dosage Modification
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 and amivantamab 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. Grade 2: Initiate supportive care management. 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. 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. 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.
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.

Special Populations

Hepatic Impairment

Mild (total bilirubin ≤ 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: No dosage adjustment needed.

Renal Impairment

Mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] 30–89 mL/min): No dosage adjustment needed.

Geriatric Patients

No specific dosage recommendations.

Cautions for Lazertinib Mesylate

Contraindications

None.

Warnings/Precautions

Venous Thromboembolic Events

Serious and potentially fatal VTE, including DVT and PE, have occurred, primarily within the first 4 months of therapy.

Administer prophylactic anticoagulation for the first 4 months of treatment; use of vitamin K antagonists not recommended.

Monitor for signs and symptoms of VTE and treat as medically appropriate. If VTE occurs, withhold lazertinib and amivantamab therapy based on severity.

Interstitial Lung Disease/Pneumonitis

ILD or pneumonitis may occur.

Monitor for new or worsening symptoms suggestive of ILD/pneumonitis, such as dyspnea, cough, and fever. Immediately withhold lazertinib and amivantamab if ILD/pneumonitis is suspected, and discontinue permanently if confirmed.

Dermatologic Adverse Reactions

Rash is common, reported by 86% of patients in clinical trials; median time of onset, 14 days (range: 1 to 556 days). Other severe dermatologic reactions include acneiform dermatitis, pruritus, and dry skin have occurred.

Patients should use an alcohol-free emollient and limit sun exposure during treatment and for 2 months after, wearing protective clothing and broad-spectrum sunscreen to reduce dermatologic risks. Consider prophylactic measures, such as oral antibiotics, to reduce dermatologic risks.

If skin reactions develop, administer topical corticosteroids and antibiotics. For Grade 3 reactions, administer oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, reduce the dose, or permanently discontinue lazertinib and amivantamab based on severity.

Ocular Toxicity

Ocular toxicity, including keratitis, may occur.

Withhold, reduce the dose, or permanently discontinue amivantamab and continue lazertinib based on severity.

Promptly refer patients with new or worsening eye symptoms to an ophthalmologist.

Embryofetal Toxicity

Lazertinib may cause fetal harm when given to pregnant women, as animal studies showed reduced embryo-fetal survival, lower fetal weight in rats, and malformations in rabbits at exposures near human levels.

Advise females of reproductive potential to use effective contraception during lazertinib treatment and for 3 weeks after last dose; advise males with partners of reproductive potential to do the same.

Specific Populations

Pregnancy

May cause fetal harm based on mechanism of action and findings from animal studies.

Lactation

There are no data on the presence of lazertinib or its metabolites in human milk or effects on the breastfed child or on milk production.

Females and Males of Reproductive Potential

May cause fetal harm. Confirm pregnancy status before initiating treatment.

Advise females to use contraception during treatment and for 3 weeks after the last dose.

Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 weeks after the last dose.

Refer to the amivantamab prescribing information for recommended duration of contraception during treatment with amivantamab.

Pediatric Use

Safety and effectiveness not established.

Geriatric Use

No safety or effectiveness differences observed between patients ≥65 years of age and younger patients.

Hepatic Impairment

No dosage adjustment needed in 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; effects in severe hepatic impairment unknown.

Renal Impairment

No dose adjustment needed in mild or moderate renal impairment (eGFR 30–89 mL/min); effects in severe renal impairment unknown.

Common Adverse Effects

Most common adverse reactions (≥20%) of lazertinib in combination with amivantamab: rash, nail toxicity, infusion-related reaction (amivantamab), musculoskeletal pain, edema, stomatitis, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, ocular toxicity.

Most common Grade 3 or 4 laboratory abnormalities (≥2%) of lazertinib in combination with amivantamab: decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, increased GGT, increased magnesium.

Drug Interactions

CYP3A4 substrate; inhibits CYP3A4, UDP-glucuronosyltransferase 1A1 (UGT1A1), breast cancer resistance protein (BCRP), and organic cation transporter 1 (OCT1).

Weak CYP3A4 inhibitor.

Does not induce CYP1A2, CYP2B6, or cytochrome CYP3A4.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Strong or moderate CYP3A4 inducers: Avoid use; consider alternative medications.

CYP3A4 substrates: May increase exposure of CYP3A4 substrates; monitor for adverse reactions.

Drugs Affecting or Affected by Transport Systems

BCRP substrates: May increase exposure of BCRP substrates; monitor for adverse reactions.

Gastric Acid Reducing Drugs

When administered with gastric acid reducing drugs, lazertinib peak plasma concentrations and AUC remained unchanged.

Specific Drugs

Drug	Interaction	Comments
Efavirenz	Predicted to decrease lazertinib peak concentration by 32% and AUC by 44%	Avoid use; consider alternative medications
Itraconazole	Increased lazertinib peak concentration by 20% and AUC by 50%	Monitor for adverse reactions
Metformin	No clinically significant pharmacokinetic changes
Midazolam	Increased midazolam peak concentration by 40% and AUC by 50%	Monitor for adverse reactions
Raltegravir	No clinically significant pharmacokinetic changes
Rifampin	Decreased lazertinib peak concentration by 72% and AUC by 83%	Avoid use; consider alternative medications
Rosuvastatin	Increased rosuvastatin peak concentration by 40% and AUC by 50%	May increase risk of adverse reactions; monitor closely

Lazertinib Mesylate Pharmacokinetics

Absorption

Plasma Concentration

Median time to peak plasma concentration: 2 to 4 hours.

A high-fat meal did not significantly affect lazertinib pharmacokinetics compared to fasting.

Distribution

Plasma Protein Binding

99.2%

Elimination

Elimination Route

Primarily through glutathione conjugation (enzymatic or non-enzymatic) with CYP3A4 as a minor pathway. Excretion occurs mainly via feces (86%) with minimal unchanged drug in urine (<0.2%).

Half-life

3.7 days

Stability

Storage

Oral

Tablets

Store at 20-25°C; excursions permitted between 15-30°C.

Actions

A third generation kinase inhibitor of epidermal growth factor receptor (EGFR) and an antineoplastic agent.
In human NSCLC cells and mouse xenograft models of EGFR exon 19 deletions or exon 21 L858R substitution mutations, lazertinib demonstrated anti-tumor activity. 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.

Advice to Patients

Advise patients to read the FDA-approved patient labeling.
Advise patients of the risk of serious venous thromboembolic events, including deep vein thrombosis and pulmonary embolism, and recommend prophylactic anticoagulants for the first four months of treatment. Advise immediate contact with a healthcare provider if signs and symptoms of VTE occur.
Advise patients of the risks of ILD/pneumonitis. Advise patients to immediately contact their healthcare provider for new or worsening respiratory symptoms.
Advise patients of the risk of skin-related adverse reactions with lazertinib. Recommend applying an alcohol-free emollient cream to reduce this risk. Advise patients to limit direct sun exposure during treatment and for 2 months afterward, use broad-spectrum UVA/UVB sunscreen, and wear protective clothing.
Advise patients of the risk of ocular adverse reactions and to contact their ophthalmologist if they develop eye symptoms. Advise discontinuation of contact lenses until symptoms are evaluated.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise female patients of reproductive potential about the potential risk to a fetus with lazertinib, to use effective contraception during treatment and for 3 weeks after the last dose, and to inform their healthcare provider of any known or suspected pregnancy. Refer to the amivantamab prescribing information for recommended duration of contraception during treatment with amivantamab.
Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 weeks after the last dose.
Advise patients not to breastfeed during treatment with lazertinib and for 3 weeks after the last dose. Refer to the amivantamab prescribing information for lactation information during treatment with amivantamab.
Inform patients of other important precautionary information.

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].

Preparations

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]