New EGFR-targeting Combination Therapy for Lung Cancer
The FDA approved lazertinib plus amivantamab-vmjw for the treatment of certain EGFR-mutated lung cancers.
The U.S. Food and Drug Administration (FDA) has approved lazertinib (Lazcluze), in combination with amivantamab-vmjw (Rybrevant), for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that harbors an exon 19 deletion or L858R mutation in the epidermal growth factor receptor (EGFR) gene.
Lazertinib is a targeted therapy that inhibits mutant forms of EGFR. Amivantamab-vmjw is another targeted therapy called a bispecific antibody that also targets EGFR, but it additionally blocks the activity of MET, a receptor that can kickstart the same cell growth and proliferation processes. Amplification or mutations in MET are common ways tumors develop resistance to EGFR inhibitors, so blocking both proteins together may prevent or overcome treatment resistance.
Amivantamab-vmjw has been previously approved as first-line and subsequent-line treatment of certain patients with NSCLC that harbors insertion mutations in exon 20 of EGFR, but this is its first approval for tumors with exon 19 deletions or L858R mutations. This is the first FDA approval for lazertinib.
The approval was based on results from the randomized, active-controlled, multicenter phase III MARIPOSA clinical trial. Researchers enrolled 1,074 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R mutations who had not received any prior systemic therapies for advanced disease. Patients were randomly assigned (2:2:1) to receive lazertinib plus amivantamab-vmjw; osimertinib (Tagrisso), another EGFR inhibitor approved for this patient population; or lazertinib alone.
Patients treated with lazertinib plus amivantamab-vmjw lived for a median of 23.7 months without their cancer progressing, compared to 16.6 months for those treated with osimertinib. Researchers did not have enough data to determine whether patients in the lazertinib plus amivantamab-vmjw arm lived longer overall than those in the osimertinib arm, but trends in the data did not suggest lazertinib plus amivantamab-vmjw correlated with shorter survival.
The recommended dose of lazertinib is 240 mg by mouth once daily. The recommended dose of amivantamab-vmjw is 1,050 mg for patients weighing less than 80 kg and 1,400 mg for patients weighing 80 kg or more. Amivantamab is administered via intravenous infusion every week for five weeks, a break for week 6, and every two weeks after that beginning with week 7. The combination can be given until disease progression or unacceptable toxicity.
NSCLC accounts for more than 80% of lung cancer cases. The incidence of EGFR mutations in NSCLC varies widely based on race, with patients of Asian descent having the highest incidence and patients of European descent having the lowest incidence; nearly half of EGFR mutations in NSCLC are exon 19 deletions and 35% are L858R mutations. According to federal statistics, it was estimated that 234,580 individuals would be diagnosed with lung cancer and 125,070 patients would die of the disease in the United States in 2024.
The FDA rendered its decision on August 19, 2024.
