Combination of Amivantamab and Lazertinib to Treat Non–Small Cell Lung Cancer
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on November 26th, 2025
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Chemotherapies that target the epidermal growth factor receptor signaling pathway (EGFR-TKIs) have been central to treating non–small cell lung cancer (NSCLC). However, even the most advanced third-generation agents offer only moderate benefit, with median survival around three years and a 5-year survival rate below 20%. Resistance to current therapies continues to emerge, highlighting the need for new treatment strategies. With support from Janssen, researchers conducted a study evaluating the combined use of amivantamab and lazertinib in NSCLC.
The phase 3 trial enrolled 858 participants with locally advanced or metastatic NSCLC. Tumor genetic testing showed that approximately 60% had exon 19 deletions, while the remaining patients carried the leucine-to-arginine substitution at position 858. Participants were randomly assigned to receive either osimertinib alone or a combination of amivantamab and lazertinib. Both osimertinib and lazertinib are third-generation EGFR-TKIs, while amivantamab is a bispecific EGFR–MET antibody designed to inhibit tumor growth driven by both EGFR and MET signaling pathways.
After a median follow-up of 37.8 months, treatment with amivantamab plus lazertinib was associated with a 25% reduction in the risk of death compared with osimertinib. The 3-year overall survival rate was also higher in the combination group at 60%, compared with 51% in the osimertinib group. However, adverse events were more common among patients receiving the combination therapy: 80% experienced significant side effects, versus 52% in the osimertinib group.
The phase 3 trial enrolled 858 participants with locally advanced or metastatic NSCLC. Tumor genetic testing showed that approximately 60% had exon 19 deletions, while the remaining patients carried the leucine-to-arginine substitution at position 858. Participants were randomly assigned to receive either osimertinib alone or a combination of amivantamab and lazertinib. Both osimertinib and lazertinib are third-generation EGFR-TKIs, while amivantamab is a bispecific EGFR–MET antibody designed to inhibit tumor growth driven by both EGFR and MET signaling pathways.
After a median follow-up of 37.8 months, treatment with amivantamab plus lazertinib was associated with a 25% reduction in the risk of death compared with osimertinib. The 3-year overall survival rate was also higher in the combination group at 60%, compared with 51% in the osimertinib group. However, adverse events were more common among patients receiving the combination therapy: 80% experienced significant side effects, versus 52% in the osimertinib group.