Lazcluze

In combination with amivantamab-vmjw for 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.

Recommended dose: 240 mg orally once daily in combination with amivantamab-vmjw. For amivantamab dose: administer IV weekly for Cycles 1–2, then every 2 weeks for Cycles 3–6, then every 4 weeks thereafter (each cycle = 4 weeks). Take lazertinib at the same time each day, with or without food.
Dose reduction: First reduction to 160 mg; second to 80 mg. Discontinue if unable to tolerate 80 mg.

Tablets: 40 mg, 80 mg, 240 mg (film-coated)

None established in prescribing information.

• Infusion-Related Reactions (IRR) with amivantamab: IRR occurred in 66% of patients. Pre-medicate before each amivantamab infusion.
• Interstitial Lung Disease (ILD)/Pneumonitis: Occurred in 3.3% of patients. Withhold and investigate; permanently discontinue if confirmed Grade 3–4.
• Dermatologic Adverse Reactions: Rash, paronychia, and other skin toxicities are common with the combination. Dermatologic supportive care recommended.
• Venous Thromboembolism (VTE): VTE including pulmonary embolism occurred. Consider VTE prophylaxis per guidelines.
• Ocular Toxicity: Keratitis and other ocular effects reported. Promptly refer to ophthalmology for new symptoms.
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise effective contraception.

Rash (84%), Paronychia (58%), Edema (53%), Nausea (35%), Fatigue (33%), Diarrhea (31%), Stomatitis (29%), ILD/Pneumonitis (3%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Strong CYP3A4 inducers: Decrease lazertinib exposure; avoid concomitant use.
Strong CYP3A4 inhibitors: No clinically significant interaction based on available data.
P-gp or BCRP substrates: Lazertinib may increase exposure; monitor.

Can cause fetal harm. Advise females of reproductive potential to use effective contraception. Consult the full prescribing information for pregnancy risk details.

Advise women not to breastfeed during treatment and for a period after the last dose. Refer to prescribing information for duration guidance.

Safety and effectiveness in pediatric patients have not been established unless otherwise noted in the full prescribing information.

Dose modifications for organ impairment are specified in the complete prescribing information.

Lazertinib is a third-generation, brain-penetrant, irreversible EGFR tyrosine kinase inhibitor. It selectively inhibits EGFR mutations including exon 19 deletions, L858R, and T790M while sparing wild-type EGFR. When combined with amivantamab (a bispecific EGFR-MET antibody), dual targeting of EGFR provides comprehensive suppression of tumor signaling.

Tmax: ~2 hours. Bioavailability: ~71%. Protein binding: ~97%. Metabolized by CYP3A4 and other pathways. Half-life: ~54 hours. Elimination: feces (~88%), urine (~4%). Steady state: ~8 days.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• MARIPOSA — Lazertinib + amivantamab vs osimertinib in first-line EGFR-mutant advanced NSCLC. Phase III, n=1074.
  🔬 NCT04487080 ↗📄 Primary Publication ↗
• MARIPOSA-2 — Amivantamab + lazertinib + chemotherapy vs chemotherapy in EGFR-mutant NSCLC after osimertinib. Phase III, n=657.
  🔬 NCT04988295 ↗📄 Primary Publication ↗

Lazcluze has FDA-approved indications across the following cancer types covered on CancerDrugEvidence: