FDA Approves Amivantamab Plus Lazertinib as First-Line Treatment for Advanced EGFR-Mutated NSCLC

The US Food and Drug Administration (FDA) has approved amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) for the first-line treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test, according to an announcement from Johnson & Johnson.

With this FDA approval, the combination treatment becomes “the first and only multitargeted, chemotherapy-free combination regimen with demonstrated superiority versus osimertinib approved for the first-line treatment of patients with EGFR-mutated NSCLC,” company officials said in the announcement.

The FDA approval is based on results from the phase 3 MARIPOSA study. The study showed that the combination of amivantamab-vmjw plus lazertinib reduced the risk of disease progression or death by 30% compared with osimertinib in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.

The median progression-free survival was 23.7 months in patients receiving the combination therapy and 16.6 months in those receiving osimertinib. The median duration of response was 25.8 months in patients receiving amivantamab-vmjw plus lazertinib, compared with 16.7 months in those receiving osimertinib.

“The unique combination of Rybrevant and Lazcluze demonstrated superior efficacy in the first-line treatment of certain patients with EGFR-mutated advanced NSCLC, as shown with the MARIPOSA study,” Alexander Spira, MD, PhD, FACP, director of the Virginia Cancer Specialists Research Institute and study investigator, said in a statement. “Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib. This first-line therapy uses a targeted approach aiming to achieve the best possible patient outcomes while reserving chemotherapy for later stages of treatment when resistance becomes more complex.”

The MARIPOSA results were initially presented at the European Society for Medical Oncology 2023 Congress and recently published in the New England Journal of Medicine. Results presented at the 2024 American Society of Clinical Oncology Annual Meeting and published in Annals of Oncology “demonstrated the combination’s significant benefit for patients who have at least 1 high-risk feature, which represents 85% of all EGFR-mutated NSCLC cases,” officials said in the announcement.

The safety profile of amivantamab-vmjw plus lazertinib was “consistent with the profiles of the individual treatments,” and venous thromboembolic events were observed with the combination, according to the announcement. Adverse event rates “were consistent in this arm as compared [with] other Rybrevant regimens,” officials said.

Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer 2024 World Congress on Lung Cancer, which will be held in San Diego, California, September 7-10.

Source: Johnson & Johnson