Lazcluze Approved for Non-Small Cell Lung Cancer

On Aug. 20, 2024, the U.S. Food and Drug Administration (FDA) approved Janssen Biotech’s Lazcluze^™ (lazertinib) 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, as detected by an FDA-approved test. Lazcluze is an EGFR tyrosine kinase inhibitor (TKI) and Rybrevant is a bispecific EGFR-directed and mesenchymal-epithelial transition (MET) receptor-directed antibody. The recommended dose of Lazcluze is 240mg orally once daily. Rybrevant is administered as an intravenous (IV) infusion once weekly for five weeks, then every two weeks starting at week seven. The first dose should be split, with half given on day one and the other half given on day two. The recommended dose of Rybrevant in patients weighing less than 80kg (approximately 176 pounds) is 1050mg and those weighing 80kg or more should receive 1400mg. Patients should be given an anticoagulant to prevent blood clots for the first four months of treatment. The launch date and pricing information have not yet been announced. Full prescribing information for Lazcluze can be found here. Updated prescribing information for Rybrevant can be found here.

At a Glance

• Brand Drug: Lazcluze^™ (lazertinib)
• Manufacturer: Janssen Biotech
• Date Approved: August 20, 2024
• Indication: in combination with Rybrevant (amivantamab-vmjw) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test
• Dosage Forms Available: 80mg and 240mg tablets
• Launch Date: To be determined
• Estimated Annual Cost: Not yet available
• According to the American Cancer Society, approximately 235,000 new cases of lung cancer are diagnosed each year in the U.S. and about 85% are NSCLC. EGFR mutations exist in 10-15% of Western patients and 40-50% of Asian patients. EGFR exon 19 deletions or exon 21 L858R substitution mutations are the most common EGFR mutations.
• Approval was based on results from the Phase III MARIPOSA trial in which patients treated first-line with Rybrevant and Lazcluze had a 30% reduced risk of disease progression or death versus Tagrisso^® (osimertinib – AstraZeneca). Additionally, patients had a duration of response of nine months or longer.
• The most common adverse events experienced by patients in the trial were rash, nail toxicity, infusion-related reactions (Rybrevant), musculoskeletal pain, stomatitis, swelling, and blood clots.
• A subcutaneous version of Rybrevant (amivantamab-vmjw and hyaluronidase) is under FDA review with an expected approval date of April 19, 2025, in combination with Lazcluze for the treatment of adults with NSCLC.
• The combination of Rybrevant and Lazcluze was approved with Priority Review.