Lazertinib — Drug Monograph

Brand names: Lazcluze

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Third-generation, irreversible, CNS-penetrant EGFR tyrosine kinase inhibitor. Selectively targets EGFR activating mutations (exon 19 deletions and L858R) and the T790M resistance mutation while sparing wild-type EGFR, thereby reducing skin and GI toxicity relative to earlier-generation TKIs. Its high blood-brain barrier penetration provides activity against CNS/brain metastases.

FDA Indications

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations — first-line, in combination with amivantamab (MARIPOSA)

Common Side Effects

• Rash/acneiform dermatitis
• Paronychia
• Diarrhea
• Stomatitis
• Dry skin/pruritus
• Fatigue
• Nausea
• Peripheral edema

Clinical Pearl

In the MARIPOSA trial, first-line lazertinib plus amivantamab improved progression-free survival versus osimertinib in EGFR-mutant (exon 19 del/L858R) advanced NSCLC, offering a chemotherapy-free combination option. The combination carries a notable VTE risk — anticoagulant prophylaxis is recommended for the first ~4 months. Both agents are CNS-active.

Related Therapies & Mechanisms

• Afatinib (Gilotrif) — Tyrosine Kinase Inhibitor · NSCLC
• Alectinib (Alecensa) — Tyrosine Kinase Inhibitor · NSCLC
• Capmatinib (Tabrecta) — Tyrosine Kinase Inhibitor · NSCLC
• Dabrafenib (Tafinlar) — Tyrosine Kinase Inhibitor · NSCLC