European Commission approves LAZCLUZE®▼ (lazertinib) in combination with RYBREVANT®▼ (amivantamab) for the first-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer

Clinical Trial Results - The Phase 3 MARIPOSA study demonstrated that amivantamab plus lazertinib significantly improved progression-free survival (PFS) compared to osimertinib, with a median PFS of 23.7 months versus 16.6 months, reducing the risk of disease progression or death by 30% [7] - Median overall survival (OS) for amivantamab plus lazertinib is expected to exceed one year compared to osimertinib, marking a clinically meaningful improvement [1][3] - The combination therapy showed a nine-month improvement in median duration of response (DOR) compared to osimertinib (25.8 months vs. 16.8 months) [7] Regulatory Approval - The European Commission (EC) approved the combination of amivantamab and lazertinib for first-line treatment of adult patients with advanced NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations [1][5] - This approval follows a Type II variation extension for amivantamab in December 2024, allowing its use in combination with lazertinib for the same indication [5] Safety Profile - The safety profile of amivantamab plus lazertinib was consistent with earlier studies, with mostly Grade 1 or 2 adverse events (AEs) [4] - Common treatment-emergent adverse events (TEAEs) included paronychia (68%), infusion-related reactions (63%), and rash (62%) [4] - The rate of discontinuation due to treatment-related AEs was 10%, and the rate of interstitial lung disease was 3% [4] Market and Industry Impact - NSCLC accounts for 85% of lung cancer cases in Europe, with EGFR mutations present in 10-15% of Western patients and 40-50% of Asian patients [14][15] - The five-year survival rate for advanced NSCLC patients with EGFR mutations treated with EGFR TKIs is less than 20%, highlighting the unmet need for improved therapies [15] - The approval of amivantamab plus lazertinib represents a significant advancement in NSCLC treatment, offering a chemotherapy-free regimen with potential to extend life expectancy [4][5] Study Design and Methodology - The MARIPOSA study enrolled 1,074 patients and evaluated amivantamab plus lazertinib versus osimertinib and lazertinib alone in first-line treatment of EGFR-mutated NSCLC [6] - The study included serial brain MRI imaging, as nearly 30% of patients develop brain metastases, and CNS events were part of the primary PFS endpoint [8] - Secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DOR), and intracranial PFS [6]