FDA Approves Lazertinib Plus Amivantamab for First-Line EGFR-Mutated NSCLC
Key Insights
The FDA has approved lazertinib (LECLAZA) in combination with amivantamab (RYBREVANT) as a first-line treatment for NSCLC (search) with EGFR (search) exon 19 deletions or exon 21 L858R substitution mutations.
The approval was based on the Phase 3 MARIPOSA study, which demonstrated a 30% reduction in the risk of disease progression or death compared to osimertinib.
The combination therapy showed a median progression-free survival of 23.7 months versus 16.6 months with osimertinib, and a longer duration of response (25.8 months vs. 16.8 months).
The U.S. Food and Drug Administration (FDA) has granted approval to lazertinib (LECLAZA, Yuhan Corporation (search)) in combination with amivantamab (RYBREVANT, Johnson & Johnson) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC (search)) harboring epidermal growth factor receptor (EGFR (search)) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test. This approval marks a significant advancement in the treatment landscape for EGFR-mutated NSCLC, offering a new chemotherapy-free option for patients.
The FDA's decision was based on the positive results from the Phase 3 MARIPOSA study. The study demonstrated that the combination of RYBREVANT plus LECLAZA reduced the risk of disease progression or death by 30% compared to osimertinib (Tagrisso), the current standard of care. The median progression-free survival (PFS) was 23.7 months in the RYBREVANT plus LECLAZA arm, compared to 16.6 months in the osimertinib arm. Furthermore, the median duration of response (DOR) was nine months longer with the combination therapy (25.8 months vs. 16.8 months). These results highlight the clinical benefit of this novel combination in extending the time patients live without disease progression.
Mechanism of Action
Lazertinib is a highly selective, brain-penetrant, third-generation oral EGFR (search) tyrosine kinase inhibitor (TKI). Amivantamab is an EGFR and MET receptor-directed bispecific antibody with immune cell-directing activity. The combination of these two agents provides a multi-targeted approach, addressing both the extra- and intracellular domains of EGFR. This dual mechanism of action is believed to contribute to the improved efficacy observed in the MARIPOSA study.
Clinical Significance
Lung cancer remains a leading cause of cancer-related deaths worldwide, with NSCLC (search) accounting for the majority of cases. EGFR (search) mutations are present in approximately 10-15% of NSCLC cases in Western populations and 30-40% in Asian populations. The approval of lazertinib plus amivantamab provides a valuable new option for these patients, offering the potential for improved outcomes compared to existing therapies. The combination's superior progression-free survival over osimertinib, as demonstrated in the MARIPOSA study, addresses a critical unmet need in the first-line treatment of EGFR-mutated NSCLC.
Yuhan Corporation's Achievement
This FDA approval represents a significant milestone for Yuhan Corporation (search), marking the first success of open innovation in its R&D investments. LECLAZA, initially approved in Korea in January 2021, has rapidly gained recognition as an effective treatment for NSCLC (search). "The FDA's approval of LECLAZA is particularly significant as it marks the first major success of R&D investment through open innovation," said Wook-Je Cho, CEO of Yuhan Corporation. "We hope this approval serves not as an endpoint but as a milestone, laying the foundation for Yuhan to achieve its goal of becoming a Global Top 50 company."