Lung cancer and lung diseases, generative AI: © Royalty-Free – stock.adobe.com
- The FDA has approved the combination of lazertinib (Lazcluze) and amivantamab-vmjw (Rybrevant) for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR Deletions of exon 19 or substitution mutations of exon 21 L858R.
- The approval is supported by results from the MARIPOSA Phase 3 study (NCT04487080).
- This combination is now the only multi-targeted regimen for both common EGFR Mutations.
The combination of lazertinib and amivantamab is now approved by the FDA for the first-line treatment of adult patients with locally advanced or metastatic NSCLC. EGFR Deletions of exon 19 or substitution mutations of exon 21 L858R.1.2
“This approval is a crucial development for patients with EGFR-mutated NSCLC, where there has been a significant unmet need for far too long,” said Jill Feldman, lung cancer survivor and co-founder of patient advocacy group EGFR Resisters, in a press release.2 “Having witnessed first-hand the remarkable evolution in lung cancer treatment, this critically important milestone offers patients and their families a novel therapeutic approach. I am thrilled that more patients can now experience progression-free survival (PFS). Advantages in the MARIPOSA study.”
With this approval, the combination is now the first and only multi-targeted, chemotherapy-free combination regimen that has been shown to be superior to osimertinib (Tagrisso) in the first-line treatment of EGFR-mutated NSCLC.
About the Phase 3 MARIPOSA study
The approval is supported by the Phase 3 MARIPOSA studyIn the randomized, active-controlled, multicenter study, 1074 patients were treated with amivanatamab plus lazertinib, lazertinib monotherapy, or osimertinib monotherapy.1 The combination regimen resulted in a statistically significant improvement in PFS, the primary endpoint, with a hazard ratio of 0.70 (95% CI, 0.58–0.85; P =.0002). The median PFS was 23.7 months (95% CI, 19.1-27.7) with the combination and 16.6 months (95% CI, 14.8-18.5) with osimertinib. At the time of the current analysis, overall survival data were not yet mature, but no trend toward worsening was observed.
Regarding safety, the most common adverse reactions occurring in at least 20% of patients were rash, nail toxicity, amivantamab infusion reactions, musculoskeletal pain, edema, stomatitis, venous thromboembolic events (VTE), paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, bleeding, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. A serious safety signal for VTE was identified and associated with lazertinib, and patients should receive prophylactic anticoagulation for the first 4 months of therapy.
“The unique combination of (amivantamab) and (lazertinib) demonstrated superior efficacy in the first-line treatment of certain patients with EGFR-mutated advanced NSCLC, as shown by the MARIPOSA study,” said Alexander Spira, MD, PhD, FACPDirector of the Virginia Cancer Specialists Research Institute and study investigator, in a press release.2 “Patients now have the option of a potential new first-line standard of care with significant clinical advantages over osimertinib. This first-line therapy uses a targeted approach aimed at achieving the best possible treatment outcomes for patients while preserving chemotherapy for later treatment phases when resistance becomes more complex.”
