Lazcluze 80 mg Tablet

Description

Lazcluze (lazertinib) is a third-generation, brain-penetrant EGFR tyrosine kinase inhibitor (TKI) approved for first-line treatment of EGFR-mutated non–small cell lung cancer (NSCLC) in adults, used in combination with Rybrevant (amivantamab)

Benefits

• Extended progression-free survival (PFS): In the MARIPOSA Phase 3 trial, Lazcluze + Rybrevant achieved median PFS of 23.7 months vs 16.6 months with osimertinib (HR 0.70; p = 0.0002) 

• Improved overall survival (OS): Final MARIPOSA analysis showed significant OS benefit, with projected >1 year longer OS compared to osimertinib (HR 0.75; p < .005) 

• Brain metastasis control: Demonstrated intracranial PFS of ~25.4 months vs 22.2 months—showing robust CNS activity 

• Chemotherapy-free: First multitargeted regimen without traditional chemotherapy showing superior efficacy vs standard care 

Indications and Usage

• For adults with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations, detected by an FDA-approved test

• Used in combination with amivantamab (Rybrevant) as a multitargeted, chemotherapy-free regimen

How it Works

Lazcluze selectively inhibits mutant EGFR-driven tyrosine kinases, blocking the uncontrolled proliferation of cancer cells. Its ability to penetrate the brain helps control intracranial disease. When used with amivantamab—which targets both EGFR and MET via a bispecific antibody—it provides a dual blockade of key oncogenic pathways 

Dosage & Administration

• Lazcluze 80 mg, orally once daily, with or without food

• Rybrevant dosing: Weekly for first four infusions (1050 mg for <80 kg; 1400 mg for ≥ 80 kg), then every 2 weeks 

Side Effects

Common (≥ 20% incidence with amivantamab):

Rash, fatigue, diarrhea, constipation, nausea, COVID-19 infection, stomatitis, bleeding events, paronychia, infusion-related reactions (Rybrevant), musculoskeletal pain, edema, decreased appetite, paresthesia, dry/itchy skin, ocular symptoms, changes in laboratory parameters 

Serious Adverse Events:

• Venous thromboembolic events (VTE): Deep vein thrombosis/pulmonary embolism occurred; prophylactic anticoagulation recommended for first 4 months 

• Pneumonitis or interstitial lung disease: May be fatal; monitor for new/worsening respiratory symptoms

• Dermatologic toxicity: Severe rash, pruritus, dryness; sun protection and dermatologic care are advised 

• Ocular issues: Corneal inflammation, visual disturbances—discontinue contact lenses until ophthalmologic evaluation

Warning and Precaution

• Thrombosis risk: Implement prophylaxis for the initial 4 months

• Pulmonary toxicity: Monitor for pneumonitis symptoms

• Severe skin reactions: Recommend moisturizers, sun protection, dermatologic consultation

• Ocular toxicity: Prompt ophthalmologic evaluation recommended for eye symptoms; suspend contact use during treatment

• Infection risk: Vigilance for COVID-19 & other infections; manage per guidelines

Clinical Trial & Approvals

• MARIPOSA Phase 3 trial (NCT04487080): 1,074 patients randomized to combination vs osimertinib and lazertinib monotherapy arms 

• Primary endpoint (PFS): Combination reduced progression risk by 30% (HR 0.70; median 23.7 vs 16.6 months) 

• Secondary endpoint (OS): Final analysis displayed significant survival benefit (HR 0.75; median OS not reached vs ~36.7 months) 

• Approval milestones:

  • U.S. FDA: August 19–20, 2024, for use with Rybrevant 

  • European Commission: late 2024 / early 2025; South Korea: January 2021 (monotherapy approvals earlier)