FDA Approved Lazertinib Plus Amivantamab for Advanced Non-Small Cell Lung Cancer With EGFR Mutations

On August 19, 2024, the US Food and Drug Administration (FDA) approved lazertinib plus amivantamab for first-line treatment of patients 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. This regulatory decision was based on results from the MARIPOSA trial.

This multicenter, randomized, active-controlled phase 3 trial enrolled 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC who had not previously received systemic treatment for advanced disease. Patients were randomized on a 2-to-2-to-1 basis to receive lazertinib plus amivantamab; osimertinib monotherapy; or lazertinib monotherapy until disease progression or unacceptable toxicity. It is noted that lazertinib on its own is not an approved regimen for NSCLC. The major efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review comparing the lazertinib plus amivantamab arm and the osimertinib arm. A key secondary outcome measure was overall survival (OS).

The median PFS of the lazertinib and amivantamab arm was 23.7 months vs 16.6 months in the osimertinib monotherapy arm, representing a statistically significant improvement (hazard ratio, 0.70; 95% confidence interval, 0.58 to 0.85; P = .0002). At the time of analysis, OS data was immature, however no trend toward detriment was  observed.

The most common adverse reactions, occurring in ≥ 20% of patients, were rash, nail toxicity, infusion-related reactions attributed to amivantamab, musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, hemorrhage, dry skin, decreased appetite, pruritis, nausea, and ocular toxicity. There was a serious safety signal of venous thromboembolic events (VTE) observed with lazertinib in combination with amivantamab, and prophylactic anticoagulation are recommended for the first 4 months of therapy.

The recommended dose of lazertinib is 240 mg once daily in combination with amivantamab with or without food. The recommended amivantamab dose is based on baseline body weight.

Source:

FDA approves lazertinib with amivantamab-vmjw for non-small cell lung cancer. United States Food and Drug Administration. Accessed on August 19, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lazertinib-amivantamab-vmjw-non-small-lung-cancer