Lazertinib

LAZCLUZE, in combination with amivantamab, is indicated 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. LAZCLUZE 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 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 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.

The recommended dosage of LAZCLUZE is 240 mg orally once daily with or without food, given in combination with amivantamab. Continue treatment until disease progression or unacceptable toxicity. Administer LAZCLUZE any time prior to amivantamab when given on the same day. Refer to the amivantamab prescribing information for recommended amivantamab dosing information. Administer prophylactic and concomitant medications to reduce the risk of dermatologic adverse reactions. Administer anticoagulant prophylaxis to reduce the risk of venous thromboembolic events (VTE) for the first four months of treatment.

None. None.

Venous Thromboembolic Events (VTE): Prophylactic anticoagulation is recommended for the first four months of treatment. Monitor for signs and symptoms of VTE and treat as medically appropriate. Withhold LAZCLUZE and amivantamab based on severity. Once anticoagulant treatment has been initiated, resume LAZCLUZE and amivantamab at the same dose at the discretion of the healthcare provider. Permanently discontinue amivantamab and continue LAZCLUZE for recurrent VTE despite therapeutic anticoagulation. Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening symptoms indicative of ILD/pneumonitis. Withhold LAZCLUZE and amivantamab in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. Dermatologic Adverse Reactions: Can cause severe rash including acneiform dermatitis.

The following adverse reactions are discussed elsewhere in the labeling: Venous Thromboembolic Events Interstitial Lung Disease/Pneumonitis Dermatologic Adverse Reactions Hepatotoxicity Ocular Toxicity LAZCLUZE in Combination with Amivantamab The most common adverse reactions (≥ 20%) 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. The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, increased GGT, and increased magnesium.

Strong and moderate CYP3A4 inducers: Avoid concomitant use. Effect of Other Drugs on LAZCLUZE CYP3A4 Inducers Avoid concomitant use of LAZCLUZE 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.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).