Patients on the new combination went a median of 23.7 months before their lung cancer grew. Those on osimertinib alone went 16.6 months. That gap, measured in the MARIPOSA trial, is what led the U.S. Food and Drug Administration in August 2024 to approve lazertinib (Lazcluze) together with amivantamab-vmjw (Rybrevant).
The pairing is cleared as a first treatment for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC). Their tumors must carry EGFR exon 19 deletions or exon 21 L858R substitution mutations, confirmed by an FDA-approved test. Lazertinib is a kinase inhibitor aimed at the epidermal growth factor receptor. It is a tablet, while amivantamab is given by infusion. Janssen Biotech makes both.
The trial
MARIPOSA enrolled 1074 people who had received no earlier systemic therapy for advanced disease. They were randomized 2:2:1 to lazertinib with amivantamab, osimertinib alone, or lazertinib alone, a regimen not approved for NSCLC. Each person stayed on treatment until the disease progressed or side effects became intolerable.
The FDA’s approval was based on data from 858 adults. The trial ran at 204 sites in 26 countries, but only 12 of the 858 were enrolled in the United States.
The main measure was progression-free survival, judged by a blinded independent central review. The hazard ratio was 0.70 (95% CI: 0.58, 0.85; p-value=0.0002), which works out to a 30% lower risk of progression or death. Overall survival results were immature, with only 55% of the pre-specified deaths recorded, but there was no sign of a negative trend.
Risks and dosing
Side effects striking 20% or more of patients 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.
The clot risk is significant enough that preventive anticoagulation is recommended for the first four months of therapy.
The dose of lazertinib is 240 mg by mouth once a day, with or without food. Amivantamab dosing depends on the patient’s baseline body weight.
Other countries
South Korea approved lazertinib in January 2021, sold there as Leclaza. In November 2024 the European Medicines Agency’s human medicines committee gave a positive opinion on Lazcluze with amivantamab, and the European Union authorized it in January 2025. Janssen-Cilag International NV is the applicant.
Sources
- Lazertinib – Wikipedia
- Lazertinib with amivantamab-vmjw is approved by the USFDA for non-small lung cancer
