EC Approves Amivantamab Plus Lazertinib for First-Line EGFR-Mutated NSCLC
核心洞察
The European Commission has approved amivantamab plus lazertinib for first-line treatment of EGFR (搜索)-mutated non-small cell lung cancer (搜索) (NSCLC (搜索)).
The approval is based on the Phase 3 MARIPOSA trial, which showed superior progression-free survival compared to osimertinib.
The combination therapy reduced the risk of disease progression or death by 30% compared to osimertinib monotherapy.
The European Commission (EC) has granted marketing authorization for amivantamab (Rybrevant), in combination with lazertinib (Lazcluze), for the first-line treatment of adult patients with advanced non-small cell lung cancer (搜索) (NSCLC (搜索)) harboring epidermal growth factor receptor (EGFR (搜索)) exon 19 deletions or exon 21 L858R substitution mutations. This decision marks a significant advancement in the treatment landscape for EGFR-mutated NSCLC, offering a chemotherapy-free regimen with improved outcomes. The approval was announced by Janssen-Cilag International NV, a Johnson & Johnson company.
MARIPOSA Trial Results
The EC's approval is based on the Phase 3 MARIPOSA trial (NCT04487080), a randomized study evaluating amivantamab plus lazertinib versus osimertinib as a first-line treatment. The trial enrolled 1,074 patients with locally advanced or metastatic NSCLC (搜索) with EGFR (搜索) exon 19 deletions or exon 21 L858R substitution mutations. The primary endpoint of the study was progression-free survival (PFS), assessed by blinded independent central review (BICR).
At a median follow-up of 22 months, the combination of amivantamab and lazertinib demonstrated a statistically significant and clinically meaningful improvement in PFS compared to osimertinib. The median PFS was 23.7 months (95% CI, 19.1-27.7) in the amivantamab plus lazertinib arm, compared to 16.6 months (95% CI, 14.8-18.5) in the osimertinib arm (HR, 0.70; 95% CI, 0.58-0.85; P < .001). This represents a 30% reduction in the risk of disease progression or death.
Longer-term follow-up data, presented at the IASLC 2024 World Conference on Lung Cancer, showed a favorable overall survival (OS) trend for amivantamab plus lazertinib versus osimertinib. At three years (median follow-up of 31.1 months), 61% of patients receiving amivantamab plus lazertinib were alive compared to 53% of those treated with osimertinib (HR=0.77; 95 percent CI, 0.61-0.96; nominal P =0.019).
Safety Profile
The safety profile of the amivantamab and lazertinib combination was consistent with previous reports from Phase 1-2 studies. Most adverse events (AEs) were Grade 1 or 2 in severity and were manageable with dose interruptions, reductions, and supportive care. The most common treatment-emergent adverse events (TEAEs) of any grade were paronychia (68%), infusion-related reactions (63%), and rash (62%). Grade 3 or higher TEAEs included rash (15%), paronychia (11%), and dermatitis acneiform (8%). The rate of discontinuation of all study treatments due to treatment-related AEs for the amivantamab combination was 10%. The rate of interstitial lung disease (including pneumonitis) was less than three percent in both arms.
Expert Commentary
"For people living with advanced NSCLC (搜索) harbouring EGFR (搜索) mutations, new treatment options are urgently needed in the first-line setting," said Enriqueta Felip, M.D., Ph.D, head of the thoracic cancer unit at Vall d’Hebron University Hospital, Barcelona, Spain. She added, "The amivantamab and lazertinib combination has shown significant progression-free survival improvements in patients with previously untreated EGFR-mutated advanced NSCLC, including those with brain metastases, compared to osimertinib monotherapy. This approval by the European Commission offers the potential to broaden first-line treatment options and provide a new standard of care for eligible patients."
About Amivantamab and Lazertinib
Amivantamab is a fully-human EGFR (搜索)-MET bispecific antibody that targets tumors with activating and resistance EGFR mutations and MET mutations and amplifications, and by harnessing the immune system. Lazertinib is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR. Janssen Biotech, Inc., has a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.
Impact on NSCLC Treatment
Lung cancer remains Europe’s biggest cancer killer, with NSCLC (搜索) accounting for 85% of all lung cancer cases. EGFR (搜索) mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients. The approval of amivantamab plus lazertinib offers a new, effective, and chemotherapy-free option for these patients, potentially improving survival outcomes and quality of life.