Officials with the FDA approved lazertinib (Lazcluze; Janssen Biotech, Inc) in combination with amivantamab-vmjw (Rybrevant; Janssen Biotech, Inc) for the first-line treatment of locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.
The combination treatment’s efficacy was studied in 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy. Patients in the MARIPOSA (NCT4487080) trial were randomly assigned in a 2:2:1 fashion to receive lazertinib in combination with amivantamab, osimertinib monotherapy, or lazertinib. Progression-free survival (PFS) and overall survival (OS) were assessed as primary and secondary outcomes, respectively.
Lazertinib with amivantamab demonstrated a statistically significant improvement in PFS compared with osimertinib (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.58-0.85; P=.0002). The median PFS was 23.7 months (95% CI, 19.1-27.7) in the lazertinib with amivantamab arm and 16.6 months (95% CI, 14.8-18.5) in the osimertinib arm.
While OS results were immature, with 55% of prespecified deaths for the final analysis reported, no trend toward a detriment was observed.
The most commonly reported adverse reactions included rash, nail toxicity, infusion-related reactions, musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.
In an August 19, 2024, statement, FDA officials noted “a serious safety signal of venous thromboembolic events (VTE) was observed with lazertinib in combination with amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy.”1
Editor’s note: This report was based on statements issued by the FDA and pharmaceutical companies mentioned in the approvals.
References
- Food and Drug Administration. FDA approves lazertinib with amivantamab-vmjwfor non-small lung cancer. August 19, 2024. Accessed August 20, 2024. www.fda.gov/drugs/resources-information-approved-drugs/fda-approveslazertinib-amivantamab-vmjw-non-small-lung-cancer