Lazcluze

/ Janssen

Recommended Dosage and Administration
The recommended dosage is 240 mg orally once daily administered in combination with amivantamab with or without food. Swallow tablets whole. Do not crush, split, or chew. Continue treatment until disease progression or unacceptable toxicity.
Administer lazertinib any time prior to amivantamab when given on the same day.
See prescribing information for full details.

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 approved test, in combination with amivantamab.

Hypersensitivity to the active substances or to any of the excipients  

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. 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. Withhold lazertinib and amivantamab based on severity [see Dosage and Administration. Once anticoagulant treatment has been initiated, resume lazertinib and amivantamab at the same dose level. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue amivantamab. Continue treatment with lazertinib at the same dose level.
Interstitial Lung Disease (ILD)/Pneumonitis
Lazertinib in combination with amivantamab can cause interstitial lung disease (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.
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 clinical research, 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. 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.
See prescribing information for full details.

Serious adverse reactions occurred in 49% of patients who received lazertinib in combination with amivantamab. Serious adverse reactions occurring in ≥ 2% of patients included VTE (11%), pneumonia (4%), rash and ILD/pneumonitis (2.9% each), COVID-19 (2.4%), and pleural effusion and infusion-related reaction (amivantamab) (2.1% each). Fatal adverse reactions occurred in 7% of patients who received lazertinib in combination with amivantamab due to death not otherwise specified (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction, and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each).
See prescribing information for full details.

Effect of Other Drugs on Lazertinib
CYP3A4 Inducers
Avoid concomitant use of lazertinib with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.
Lazertinib is a CYP3A4 substrate. Concomitant use with a strong or moderate CYP3A4 inducer decreased lazertinib concentrations, which may reduce the efficacy of lazertinib.
Effect of Lazertinib on Other Drugs
Certain CYP3A4 Substrates
Lazertinib is a weak CYP3A4 inhibitor. Concomitant use of lazertinib increased concentrations of CYP3A4 substrates, which may increase the risk of adverse reactions related to these substrates.
Certain BCRP Substrates
Lazertinib is a BCRP inhibitor. Concomitant use of lazertinib increased concentrations of BCRP substrates, which may increase the risk of adverse reactions related to these substrates.

Pregnancy: There are no available data on the use of lazertinib in pregnant women to inform a drug-associated risk. Advise pregnant women of the potential risk to a fetus.
Verify the pregnancy status of females of reproductive potential prior to initiating this medical product. Advise females of reproductive potential to use effective contraception during treatment with lazertinib and for 3 weeks after the last dose.
Males
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.
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.

Lazertinib may cause extreme fatigue. Do not drive or operate machinery if you feel very tired.