Dosage of Lazertinib

Patient Selection

Select patients with NSCLC for first-line treatment with the combination of lazertinib and amivantamab based on the presence of EGFR exon 19 deletions or exon 21 L858R substitution mutations in tumor or plasma samples. If these mutations are not detected in plasma samples, tumor tissue should be tested.

Recommended Dosage and Administration Method

The recommended dose of lazertinib is 240 mg orally once daily, administered in combination with amivantamab, which can be taken with or without food. Lazertinib tablets should be swallowed whole; do not crush, split, or chew them. Continue treatment until disease progression or unacceptable toxicity occurs.

When administering both drugs on the same day, lazertinib may be taken at any time prior to amivantamab administration. Refer to the prescribing information for amivantamab for its recommended dosage details.

Missed Dose

If a patient misses a dose of lazertinib and notices it within 12 hours, the patient should be instructed to take the missed dose. If more than 12 hours have passed, the patient should be instructed to take the next dose at the originally scheduled time.

Vomiting

If vomiting occurs at any time after taking lazertinib, the patient should be instructed to take the next dose at the originally scheduled time.

Concomitant Medications

When initiating combination treatment with lazertinib and amivantamab, thromboprophylaxis should be administered for the first four months of treatment to prevent venous thromboembolism (VTE) events. If no signs or symptoms of VTE occur within the first four months of treatment, healthcare providers may consider discontinuing thromboprophylaxis at their discretion.

When initiating combination treatment with lazertinib and amivantamab, alcohol-free (e.g., isopropanol-free, ethanol-free) moisturizers should be used. Patients should be advised to limit sun exposure, wear protective clothing, and use broad-spectrum UVA/UVB sunscreen during treatment and for 2 months after treatment to reduce the risk of cutaneous adverse reactions. Consider implementing preventive measures (e.g., oral antibiotics) to lower the risk of skin-related adverse events.

Dosage Adjustment for Adverse Reactions

The recommended dose reduction schedule for lazertinib in response to adverse reactions is as follows: For adverse reactions occurring at the dose of 240 mg once daily (one 240 mg tablet), the first dose reduction is to 160 mg once daily (two 80 mg tablets); the second dose reduction is to 80 mg once daily (one 80 mg tablet); a third dose reduction requires permanent discontinuation of lazertinib.

Recommended management and dosage adjustments for specific adverse reactions are as follows:

Venous Thromboembolism (VTE) Events:

For grade 2 or 3 events, suspend lazertinib and amivantamab. Administer anticoagulant therapy as clinically indicated. Once anticoagulant therapy is initiated, healthcare providers may decide whether to resume lazertinib and amivantamab at the same dose level.

For grade 4 events or recurrent grade 2/3 events despite therapeutic-level anticoagulation, suspend lazertinib and permanently discontinue amivantamab. Administer anticoagulant therapy as clinically indicated. Once anticoagulant therapy is initiated, healthcare providers may decide whether to continue lazertinib at the same dose level.

Interstitial Lung Disease (ILD)/Pneumonitis:

For suspected ILD/pneumonitis of any grade, suspend lazertinib and amivantamab. If ILD/pneumonitis is confirmed, permanently discontinue both lazertinib and amivantamab.

Cutaneous Adverse Reactions (including acneiform dermatitis, pruritus, dry skin):

For grade 1 reactions, initiate supportive care management. If no improvement is observed after 2 weeks, reduce the dose of amivantamab and continue lazertinib at the same dose. Reassess every 2 weeks; if there is still no improvement, reduce the dose of lazertinib until the severity is ≤ grade 1, after which healthcare providers may decide whether to restore lazertinib to its previous dose.

For grade 2 reactions, suspend lazertinib and amivantamab. Initiate supportive care management. After recovery to ≤ grade 2, resume lazertinib at the same dose or consider a dose reduction, and resume amivantamab at a reduced dose. If no improvement occurs within 2 weeks, permanently discontinue both lazertinib and amivantamab.

For grade 4 reactions (including severe bullous, vesicular, or exfoliative skin conditions), initiate supportive care management. Permanently discontinue amivantamab. Suspend lazertinib until recovery to ≤ grade 2 or baseline. After recovery to ≤ grade 2, healthcare providers may decide whether to resume lazertinib at a reduced dose.

Other Adverse Reactions:For grade 3-4 reactions, suspend lazertinib and amivantamab until the adverse reaction resolves to ≤ grade 1 or baseline. Resume both drugs at reduced doses or resume only lazertinib. If no recovery occurs within 4 weeks, consider permanent discontinuation of lazertinib and amivantamab.

FDA，2024.08