Janssen Receives CHMP Endorsement for Amivantamab-Lazertinib Combination in EGFR-Mutated Advanced NSCLC
Saturday, November 16, 2024
Janssen has announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorisation for LAZCLUZE® (lazertinib) in combination with RYBREVANT® (amivantamab).
Lung cancer remains the leading cause of cancer-related deaths globally, and EGFR-mutated NSCLC accounts for a significant proportion of cases. This new treatment combination offers a potential advance in managing the disease, delaying disease progression and reducing the reliance on chemotherapy in earlier treatment stages.
This combination is intended as a first-line treatment for adults with advanced non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or exon 21 L858R (L858R) substitution mutations. Alongside this, the CHMP also recommended a Type II extension of indication for amivantamab within the same regimen.
The recommendations are based on results from the Phase 3 MARIPOSA study, which compared the combination therapy with osimertinib for patients with locally advanced or metastatic NSCLC with EGFR mutations.
The study demonstrated a 30% reduction in the risk of disease progression or death with the combination therapy compared to osimertinib, with a median progression-free survival (PFS) of 23.7 months versus 16.6 months. A significant improvement in the median duration of response (25.8 months versus 16.8 months) was also observed.
Additional data highlighted improved outcomes in intracranial progression-free survival and a trend towards better overall survival. At a median follow-up of 31.1 months, 61% of patients on the combination therapy were alive compared to 53% on osimertinib.
The safety profile of the combination was consistent with earlier findings, with manageable side effects predominantly of Grade 1 or 2 severity. Common treatment-related side effects included skin conditions, nail inflammation, and infusion reactions. Discontinuation due to adverse events occurred in 10% of patients on the combination therapy, while interstitial lung disease was rare in both treatment groups.
The MARIPOSA study, which enrolled over 1,000 patients, included detailed monitoring of brain metastases through serial MRI scans, a measure not commonly implemented in prior studies. This provided robust insights into central nervous system involvement.
Amivantamab, a fully human bispecific antibody targeting EGFR and MET mutations, is already authorised in Europe for various NSCLC indications. Lazertinib, an oral, brain-penetrant third-generation EGFR tyrosine kinase inhibitor (TKI), is designed to target specific EGFR mutations, including T790M, while sparing normal EGFR activity.
Pending approval from the European Commission, the combination therapy could become a first-line treatment standard for patients with EGFR-mutated advanced NSCLC.
Source: jnj.com
