Lazertinib Mesylate (Monograph)

Brand name: Lazcluze
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Oct 10, 2024. Written by ASHP.

Introduction

Lazertinib, a kinase inhibitor of epidermal growth factor receptor (EGFR), is an antineoplastic agent.

Uses for Lazertinib Mesylate

Lazertinib has the following uses:

Lazertinib is a kinase inhibitor indicated in combination with amivantamab for the first-line treatment of adult patients 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.

Lazertinib Mesylate Dosage and Administration

General

Lazertinib mesylate is available in the following dosage form(s) and strength(s):

Tablets: 80 mg and 240 mg (of lazertinib).

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Select patients for the first-line treatment of NSCLC with lazertinib, in combination with amivantamab, based on the presence of EGFR exon 19 deletions or exon 21 L858R substitution mutations in tumor or plasma specimens. If these mutations are not detected in a plasma specimen, test tumor tissue.
The recommended dosage of lazertinib is 240 mg orally once daily with or without food, given 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.
Refer to the amivantamab prescribing information for recommended amivantamab dosing information.
Administer anticoagulant prophylaxis to prevent venous thromboembolic events (VTE) for the first four months of treatment.
When initiating treatment, administer alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream and encourage patients to limit sun exposure during and for 2 months after treatment, to wear protective clothing and use broad-spectrum UVA/UVB sunscreen to reduce the risk of dermatologic adverse reactions.
Refer to Full Prescribing Information for dosage modification recommendations for adverse reactions.

Cautions for Lazertinib Mesylate

Contraindications

None.

Warnings/Precautions

Venous Thromboembolic Events

Lazertinib in combination with amivantamab can cause serious and fatal venous thromboembolic events (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE). The majority of these events occurred during the first four months of therapy.

In the MARIPOSA study, VTE occurred in 36% of patients receiving lazertinib in combination with amivantamab, including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 7% of patients had VTE leading to dose interruptions of lazertinib, 0.5% of patients had VTE leading to dose reductions of lazertinib, and 1.9% of patients permanently discontinued lazertinib due to VTE. The median time to onset of VTEs was 84 days (range: 6 to 777).

Administer prophylactic anticoagulation for the first four months of treatment. The use of vitamin K antagonists is 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. Once anticoagulant treatment has been initiated, resume lazertinib and amivantamab at the same dose level at the discretion of the healthcare provider. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue amivantamab. Continue treatment with lazertinib at the same dose level at the discretion of the healthcare provider. Refer to the amivantamab prescribing information for recommended amivantamab dosage modification.

Interstitial Lung Disease (ILD)/Pneumonitis

Lazertinib in combination with amivantamab can cause interstitial lung disease (ILD)/pneumonitis.

In the MARIPOSA study, ILD/pneumonitis occurred in 3.1% of patients treated with lazertinib in combination with amivantamab, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case (0.2%) of ILD/pneumonitis and 2.9% of patients permanently discontinued lazertinib and amivantamab due to ILD/pneumonitis.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold lazertinib and amivantamab in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Dermatologic Adverse Reactions

Lazertinib in combination with amivantamab can cause severe rash including dermatitis acneiform, pruritus, and dry skin.

In the MARIPOSA study, rash occurred in 86% of patients treated with lazertinib in combination with amivantamab, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose reduction of lazertinib occurred in 19% of patients, rash leading to dose interruption of lazertinib occurred in 30% of patients, and lazertinib was permanently discontinued due to rash in 1.7% of patients.

When initiating treatment with lazertinib in combination with amivantamab, administer alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream to reduce the risk of dermatologic adverse reactions. Instruct patients to limit sun exposure during and for 2 months after treatment with lazertinib in combination with amivantamab. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen.

Consider prophylactic measures (e.g., use of oral antibiotics) to reduce the risk of dermatologic adverse reactions. If skin reactions develop, administer topical corticosteroids and topical and/or oral 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

Lazertinib, in combination with amivantamab, can cause ocular toxicity, including keratitis.

In the MARIPOSA study, ocular toxicity occurred in 16% of patients treated with lazertinib in combination with amivantamab, including Grade 3 or 4 ocular toxicity in 0.7% of patients. Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Withhold, reduce the dose or permanently discontinue amivantamab and continue lazertinib based on severity.

Embryo-fetal Toxicity

Based on findings from animal studies and its mechanism of action, lazertinib can cause fetal harm when administered to a pregnant woman. 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 based on AUC.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with lazertinib and for 3 weeks after the last dose. 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.

Specific Populations

Pregnancy

Based on findings from animal studies and its mechanism of action, lazertinib can cause fetal harm when administered to a pregnant woman. There are no available data on the use of lazertinib in pregnant women to inform a drug-associated risk. 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 based on AUC. Advise pregnant women 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 is 2% to 4% and 15% to 20%, respectively.

Lactation

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. 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. Refer to the amivantamab prescribing information for lactation information during treatment with amivantamab.

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.

Verify the pregnancy status of females of reproductive potential prior to initiating lazertinib.

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

Based on findings in animals, lazertinib may impair fertility in females and males of reproductive potential. The effects on female fertility were reversible. The effects on male testes in animal studies were not reversible within a 2-week recovery period.

Pediatric Use

The safety and effectiveness of lazertinib in pediatric patients have not been established.

Geriatric Use

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. No overall differences in safety or effectiveness were observed between patients 65 years of age and older and younger patients.

Renal Impairment

No dose adjustment is recommended in patients with mild or moderate renal impairment (eGFR 30 – 89 mL/min).

Lazertinib has not been studied in patients with severe renal impairment or end-stage renal disease (eGFR < 30 mL/min).

Hepatic Impairment

No dose adjustment is recommended in patients with mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin ≤ 1.5×ULN and any AST) or moderate (total bilirubin ≤ 1.5 to 3×ULN and any AST) hepatic impairment.

Lazertinib has not been studied in patients with severe hepatic impairment (total bilirubin > 3×ULN and any AST).

Common Adverse Effects

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, nausea, and ocular toxicity.
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.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Strong and moderate CYP3A4 inducers: Avoid concomitant use.

Actions

Mechanism of Action

Lazertinib is a kinase inhibitor of epidermal growth factor receptor (EGFR) that inhibits EGFR exon 19 deletions and exon 21 L858R substitution mutations at lower concentrations than wild-type EGFR. In human non-small cell lung cancer (NSCLC) cells and mouse xenograft models of EGFR exon 19 deletions or EGFR L858R substitution mutations, lazertinib demonstrated anti-tumor activity. Treatment with lazertinib in combination with amivantamab increased in vivo anti-tumor activity compared to either agent alone in a mouse xenograft model of human NSCLC with an EGFR L858R mutation.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).
Advise patients of the risks of serious and life threatening venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism. Advise patients that prophylactic anticoagulants are recommended to be used for the first four months of treatment. Advise patients to immediately contact their healthcare provider for signs and symptoms of venous thromboembolism.
Advise patients of the risks of interstitial lung disease (ILD)/pneumonitis. Advise patients to immediately contact their healthcare provider for new or worsening respiratory symptoms.
Advise patients of the risk of dermatologic adverse reactions. Advise patients to apply alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream to reduce the risk of dermatologic adverse reactions. Advise patients to limit direct sun exposure during and for 2 months after treatment, to use broad-spectrum UVA/UVB sunscreen, and to wear protective clothing during treatment with lazertinib. Consider prophylactic measures (e.g., use of oral antibiotics) to reduce the risk of dermatologic adverse reactions.
Advise patients of the risk of ocular adverse reactions. Advise patients to contact their ophthalmologist if they develop eye symptoms. Advise discontinuation of contact lenses until symptoms are evaluated.
Advise females of reproductive potential of the potential risk to a fetus, to use effective contraception during treatment with lazertinib and for 3 weeks after the last dose, and to inform their healthcare provider of a 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 with lazertinib and for 3 weeks after the last dose.
Advise women 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.
Advise males and females of reproductive potential of the potential risk for impaired fertility with lazertinib.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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.