Janssen-Cilag International NV, a Johnson & Johnson company, announced that the European Commission (EC) has granted marketing authorization (MA) to LAZCLUZE ^® ▼ (lazertinib), in combination with RYBREVANT ^® ▼ (amivantamab), for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations due to exon 19 deletions (ex19del) or exon 21 L858R substitutions (L858R).

The EC approval is supported by results from the Phase 3 MARIPOSA study ( NCT04487080 ) of lazertinib in combination with amivantamab versus osimertinib as first-line treatment in patients with locally advanced or metastatic NSCLC with EGFR ex19del mutations or L858R exon 21 substitution mutations. ² The study met its primary endpoint of progression-free survival (PFS). ² These data were presented during a presidential symposium at the European Society of Medical Oncology (ESMO) 2023 Congress and longer-term follow-up data presented at the International Association for the Study of Lung Cancer (IASLC) 2024 International Conference on Lung Cancer (WCLC). ^3,4

On January 7, 2025, J&J announced new positive top-line overall survival (OS) data showing that amivantamab in combination with lazertinib met the final pre-specified secondary endpoint of OS and demonstrated a clinically important and statistically significant improvement in OS compared to the current standard of care, osimertinib monotherapy.  Median OS is expected to exceed one year.  These OS top-line data will be presented at an upcoming medical meeting.

“This chemotherapy-free regimen has already demonstrated significant improvements in progression-free survival, and new high-level data suggest that it should increase median survival by one year or more in patients with untreated EGFR-mutant NSCLC compared to the current standard of care, osimertinib,” said Antonio Passaro*, MD, PhD, Medical Oncologist, Department of Thoracic Oncology, European Institute of Oncology, Milan, Italy. “These results represent a significant advance in the treatment of EGFR-mutant NSCLC. Increased survival is a critical indicator of treatment effect. The MARIPOSA study confirms the potential of this combination therapy as a first-line treatment to redefine the standard of care and deliver meaningful clinical improvements in patient outcomes.”

Previously reported results from the MARIPOSA study demonstrated that the safety profile of the combination of amivantamab and lazertinib was consistent with profiles reported from Phase 1 or 2 studies, with predominantly Grade 1 or 2 adverse events (AEs). ²  Toxicity was largely manageable with dose interruptions and reductions, along with supportive care measures, typically used in the treatment of patients with NSCLC. ²  The most common treatment-emergent AEs, regardless of grade, were paronychia (68 percent), infusion-related reactions (63 percent), and rash (62 percent). ²  The combination of amivantamab and lazertinib had higher rates of EGFR- and EMT-related AEs and venous thromboembolism compared with osimertinib, with the exception of diarrhea, which was higher for osimertinib. ²  The most common Grade 3 or higher treatment-emergent adverse events were rash (15 percent), paronychia (11 percent), dermatosis acneiform (8 percent), and pulmonary embolism (8 percent). ²  The rate of discontinuation of all study treatments due to treatment-related AEs for the combination of amivantamab and lazertinib was 10 percent. ²  The rate of interstitial lung disease (including pneumonia) was three percent in both arms. ²

“Currently, the five-year survival rate for patients with advanced NSCLC with EGFR mutations treated with EGFR tyrosine kinase inhibitors is less than 20 percent,” said Henar Hevia, Ph.D., Senior Therapeutic Area Director, EMEA Oncology. “Today’s approval marks a significant moment in lung cancer treatment, providing patients with new options through a chemotherapy-free regimen and potentially more time with their loved ones.”

This EC decision accompanies a similar EC approval in December 2024 for a variation of the extension for a Type SAII indication for the bispecific antibody amivantamab, in combination with lazertinib for the first-line treatment of adult patients with advanced NSCLC with EGFR mutations by exon 19 deletions or exon 21 L858R substitution. ⁵