FDA Approves Lazertinib and Amivantamab for NSCLC

On August 19, 2024, the Food and Drug Administration (FDA) granted approval for 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 specific epidermal growth factor receptor (EGFR) mutations. This approval applies to patients with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as confirmed by an FDA-approved test.

Efficacy and Safety

The efficacy of this combination was assessed in the MARIPOSA trial (NCT04487080), a randomized, active-controlled, multicenter study involving 1,074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC, who had not previously received systemic therapy for advanced disease. Participants were randomly assigned to receive either lazertinib with amivantamab, osimertinib monotherapy, or lazertinib monotherapy (an unapproved regimen for NSCLC) until disease progression or unacceptable toxicity.

The primary efficacy endpoint was progression-free survival (PFS), evaluated through blinded independent central review (BICR) for the comparison between the lazertinib/amivantamab combination and osimertinib. A statistically significant improvement in PFS was observed with the combination therapy, yielding a hazard ratio of 0.70 (95% confidence interval [CI]: 0.58, 0.85; p-value=0.0002). The median PFS was 23.7 months (95% CI: 19.1, 27.7) for the lazertinib/amivantamab group compared to 16.6 months (95% CI: 14.8, 18.5) for the osimertinib group.

While overall survival (OS) results were not fully mature at the time of this analysis, with only 55% of pre-specified deaths reported, no adverse trend was noted. Common adverse reactions (≥20%) associated with the combination included rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, and others. Notably, a serious safety signal for venous thromboembolic events (VTE) was observed, recommending prophylactic anticoagulation for the first four months of therapy.

The recommended dose for lazertinib is 240 mg orally once daily, with or without food, in combination with amivantamab. The amivantamab dose is determined based on the patient's baseline body weight. Detailed dosing information is available in the prescribing information.

Highlights

• FDA has approved lazertinib and amivantamab for treating advanced NSCLC with EGFR mutations.
• The approval covers first-line treatment for locally advanced or metastatic NSCLC with specific EGFR mutations.
• MARIPOSA trial showed a significant improvement in progression-free survival with the combination therapy.
• Common adverse reactions include rash and nail toxicity; a serious safety signal for venous thromboembolic events was noted.
• Prophylactic anticoagulation is recommended for the first four months of therapy.

Data source:  https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lazertinib-amivantamab-vmjw-non-small-lung-cancer