| Drug Name |
LAZCLUZE™ (lazertinib) |
| Active Ingredient |
lazertinib |
| Date of Approval |
August 20, 2024 |
| Manufacturer |
Johnson & Johnson |
| Approval Pathways and Indications |
Approval Pathway: NDA
Indication: LAZCLUZE™ is indicated in combination with RYBREVANT® (amivantamab-vmjw) 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. |
| Therapeutic Class |
tyrosine kinase inhibitor (TKI) |
| Formulation |
Tablets: 80 mg and 240 mg |
| MoA |
LAZCLUZE™ is a third-generation, brain-penetrant EGFR TKI that selectively targets EGFR mutations, including T790M, exon 19 deletions, and exon 21 L858R mutations, while sparing wild-type EGFR. It has shown anti-tumor activity in NSCLC models and increases survival by delaying cancer progression. |
| Dosing and Administration |
The recommended dosage of LAZCLUZE™ is 240 mg orally once daily with or without food, given in combination with amivantamab. Treatment should be continued until disease progression has decreased or if toxicity occurs. LAZCLUZE™ can be administered any time prior to amivantamab-vmjw when given on the same day. Anticoagulant prophylaxis should be administered to prevent venous thromboembolic events for the first four months of treatment. |
| Administered by self or by HCP |
Administered by self |
| Place in Therapy |
Lung cancer is the leading cause of cancer mortality worldwide, resulting in 1.8 million deaths each year, with NSCLC accounting for 80 to 85 percent of all cases. Of patients with EGFR-mutated NSCLC, between 25 and 39 percent never receive second-line therapy, due to disease progression and lack of treatment options. The five-year survival rate is less than 20 percent for all people with advanced EGFR-mutated NSCLC treated with current standard of care TKI monotherapy. Acquired resistance mechanisms after TKI monotherapy makes subsequent treatment more difficult.
RYBREVANT® plus LAZCLUZE™ is now the first and only multitargeted, chemotherapy-free regimen approved as a superior first-line treatment for patients with EGFR-mutated NSCLC, outperforming osimertinib. RYBREVANT® targets both EGFR and MET, engaging the immune system, while LAZCLUZE™ is a brain-penetrant, third-generation oral EGFR TKI.This combination uniquely targets both common EGFR mutations directly. |
| Expected Market Launch Date |
Data Unavailable |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
| Expected Cost |
Data Unavailable |
| Product Discontinuation |
N/A |
| Clinical Trials |
Efficacy was evaluated in MARIPOSA (NCT04487080), a randomized, active-controlled, multicenter trial of 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease. Patients were randomized (2:2:1) to receive lazertinib in combination with amivantamab, osimertinib monotherapy, or lazertinib monotherapy (an unapproved regimen for NSCLC) until disease progression or unacceptable toxicity.
The major efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review for the comparison between lazertinib with amivantamab and osimertinib. Overall survival (OS) was a key secondary outcome measure. Lazertinib with amivantamab demonstrated a statistically significant improvement in PFS compared to osimertinib with a hazard ratio of 0.70 (95% confidence interval [CI]: 0.58, 0.85; p-value=0.0002). The median PFS was 23.7 months (95% CI: 19.1, 27.7) in the lazertinib with amivantamab arm and 16.6 months (95% CI: 14.8, 18.5) in the osimertinib arm. While OS results were immature at the current analysis, with 55% of pre-specified deaths for the final analysis reported, no trend towards a detriment was observed.
The most common adverse reactions (≥20%) were rash, nail toxicity, infusion-related reactions, musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. A serious safety signal of venous thromboembolic events was observed with lazertinib in combination with amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy. |
| Sources |
Johnson & Johnson. *Rybrevant (amivantamab-vmjw) plus LAZCLUZE (lazertinib) approved in the U.S. as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer*. Published August 19, 2024. Accessed August 20, 2024. https://www.jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-approved-in-the-u-s-as-a-first-line-chemotherapy-free-treatment-for-patients-with-egfr-mutated-advanced-lung-cancer
Janssen Biotech, Inc. *LAZCLUZE (lazertinib) prescribing information*. Published August 2024. Accessed August 20, 2024. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/LAZCLUZE-pi.pdf
U.S. Food and Drug Administration. *FDA approves LAZERTINIB (lazertinib) and AMIVANTAMAB (amivantamab-vmjw) for non-small cell lung cancer*. Published August 19, 2024. Accessed August 20, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lazertinib-amivantamab-vmjw-non-small-lung-cancer
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