The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of Leclaza (lazertinib), known as Lazcluze in Europe, in combination with Rybrevant (amivantamab) for the first-line treatment of non-small cell lung cancer (NSCLC) with EGFR mutations. This decision brings the drug combination closer to market availability in Europe.
The CHMP's recommendation, announced after its November meeting, supports the use of lazertinib and amivantamab as an initial treatment for advanced NSCLC harboring epidermal growth factor receptor (EGFR) mutations. Yuhan Corp. developed Leclaza, a third-generation EGFR tyrosine kinase inhibitor (TKI), and licensed it to Johnson & Johnson globally, excluding Korea. Johnson & Johnson submitted applications to both the U.S. Food and Drug Administration (FDA) and the EMA in December 2023 for approval of the combination therapy.
The FDA approved the lazertinib and amivantamab combination in August for first-line treatment of patients with EGFR-mutation-positive metastatic NSCLC. The CHMP's positive opinion is a crucial step toward final EMA approval, which is anticipated in late 2024 or early 2025. Yuhan anticipates that EMA approval will bolster lazertinib's position in the global lung cancer treatment market.
Clinical Evidence and Guidelines
Market analysts are closely watching to see if this combination therapy will establish itself as the new standard of care in Europe. The American Society of Clinical Oncology (ASCO) recently updated its guidelines for treating advanced NSCLC with EGFR mutations, recommending Tagrisso (osimertinib) monotherapy as the primary first-line treatment. However, the guidelines suggest that combinations, such as osimertinib with platinum-based chemotherapy or lazertinib with amivantamab, may also be considered.
The ASCO recommendation is based on the FLAURA 2 and MARIPOSA studies. The MARIPOSA study demonstrated a significant improvement in progression-free survival (PFS) in the lazertinib plus amivantamab arm compared to osimertinib alone (23.7 months vs. 16.6 months, hazard ratio [HR] 0.70, P<0.001).
Safety Considerations
While the MARIPOSA study showcased promising efficacy, the combination of amivantamab and lazertinib was associated with a higher incidence of grade 3 or higher treatment-related adverse events (75 percent) compared to osimertinib monotherapy (43 percent). This highlights the necessity for careful toxicity management when using this combination therapy.
