FDA approves lazertinib with amivantamab-vmjw for non-small lung cancer

On August 19, 2024, the Food and Drug Administration 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.

Full prescribing information for Lazcluze and Rybrevant will be posted on Drugs@FDA. 

Efficacy and Safety

Efficacy was evaluated in MARIPOSA (NCT04487080), a randomized, active-controlled, multicenter trial of 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease. Patients were randomized (2:2:1) to receive lazertinib in combination with amivantamab, osimertinib monotherapy, or lazertinib monotherapy (an unapproved regimen for NSCLC) until disease progression or unacceptable toxicity.

The major efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR) for the comparison between lazertinib with amivantamab and osimertinib. Overall survival (OS) was a key secondary outcome measure. Lazertinib with amivantamab demonstrated a statistically significant improvement in PFS compared to osimertinib with 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) 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 at the current analysis, with 55% of pre-specified deaths for the final analysis reported, no trend towards a detriment was observed.

The most common adverse reactions (≥20%) were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. 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.

The recommended lazertinib dose is 240 mg orally once daily administered in combination with amivantamab with or without food. The recommended amivantamab dose is based on baseline body weight. See the prescribing information for specific dosing information.

Expedited Programs

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Switzerland’s Swissmedic, and United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). The application reviews are ongoing at the other regulatory agencies.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.  

This application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

Follow the Oncology Center of Excellence on X:  @FDAOncology.