Lazertinib With Amivantamab Approved by FDA for Use in NSCLC

The first-line treatment of locally advanced metastatic non-small cell lung cancer (NSCLC) referred to as lazertinib (LAZCLUZE), taken in combination with amivantamab-vmjw (RYBREVANT), was approved for use by the FDA on August 19, 2024.¹ This treatment can be used in patients with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.

The approval of this treatment was based on the MARIPOSA trial, which was randomized, active-controlled, and multicenter. There were 1074 patients included in the study, all of whom had exon 19 deletion or exon 21 L858R substitution; all patients had not previously received systemic therapy. Patients were randomized into 3 groups, with 1 group receiving lazertinib in combination with amivantamab, another group receiving osimertinib monotherapy, and the last group taking lazertinib monotherapy. Treatment only ceased if their disease progressed or if they had unacceptable toxicity.

Progression-free survival acted as the primary outcome evaluated with overall survival (OS) acting as a secondary outcome. A statistically significant improved in PFS was found in patients who used lazertinib with amivantamab when compared with patients who used osimertinib (HR, 0.70; 95% CI, 0.58-0.85). The patients using osimertinib had a median PFS of 16.6 months (95% CI, 14.8-18.5) compared with 23.7 months (95% CI, 19.1-27.7) in patients using lazertinib with amivantamab. There was no trend towards a detriment when reporting 55% of the pre-specified deaths.

Lazertinib with amivantamab can be used as a first-line treatment in patients with NSCLC | Image credit: Sebastian Kaulitzki - stock.adobe.com

The treatment was also shown to significantly reduce the risk of disease progression or death in different subgroups compared with patients taking osimertinib,² including a 31% reduction in patients with a history of brain metastases (18.3 vs 13.0 months; HR, 0.69; 95% CI, 0.53-0.92), 42% reduction in patients with liver metastases (18.2 vs 11.0 months; HR, 0.58; 95% CI, 0.37-0.91), 35% reduction in patients with TP53 co-mutations (18.2 vs 12.9 months; HR, 0.65; 95% CI, 0.48-0.87), 32% reduction in patients with detectable circulating tumor DNA (ctDNA) at baseline (20.3 vs 14.8 months; HR, 0.68; 95% CI, 0.53-0.86), and 51% reduction in patients without cleared ctDNA at C3D1 (16.5 vs 9.1 months; HR, 0.49; 95% CI, 0.27-0.87).

Rash, nail toxicity, edema, venous thromboembolism, infusion-related reactions, fatigue, musculoskeletal pain, paresthesia, constipation, diarrhea, hemorrhage, decreased appetite, dry skin, COVID-19, nausea, pruritus, and ocular toxicity were all reported adverse reactions in 20% or more of the patients included in the study.

Lazertinib with amivantamab is now the first and only regimen that is chemotherapy-free and multitargeted, offering a new method of treatment for patients with NSCLC. With lung cancer being the leading cause of mortality from cancer in the world and NSCLC accounting for 80% to 85% of those cases, offering a new first-line treatment is beneficial for helping to treat patients and help to target the 5-year survival rate of less than 20%.

"The unique combination of [Lazertinib with amivantamab] demonstrated superior efficacy in the first-line treatment of certain patients with EGFR-mutated advanced NSCLC as shown with the MARIPOSA study. Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib,” Alexander Spira, MD, PhD, FACP, director of Virginia Cancer Specialists Research Institute and study investigator, said in a press release.³

References

1. FDA approves Lazertinib with amivantamab-vmjw for non-small lung cancer. News release. FDA. August 19, 2024. Accessed August 20, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lazertinib-amivantamab-vmjw-non-small-lung-cancer
2. RYBREVANT (amivantamab-vmjw) plus lazertinib is the only chemotherapy-free regimen showing longer progression-free survival versus osimertinib in first-line treatment of patients with high-risk EGFR-mutated non-small cell lung cancer. News release. May 31, 2024. Accessed August 20, 2024. https://www.jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-plus-lazertinib-is-the-only-chemotherapy-free-regimen-showing-longer-progression-free-survival-versus-osimertinib-in-first-line-treatment-of-patients-with-high-risk-egfr-mutated-non-small-cell-lung-cancer
3. RYBREVANT (amivantamab-vmjw) plus LAZCLUZE (Lazertinib) approved in the U.S. as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. August 20, 2024. Accessed August 20, 2024. https://www.prnewswire.com/news-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-approved-in-the-us-as-a-first-line-chemotherapy-free-treatment-for-patients-with-egfr-mutated-advanced-lung-cancer-302226047.html