FDA Clears Lazertinib/Amivantamab for First-Line EGFR-Mutated NSCLC

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• 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 exon 19 deletions or exon 21 L858R substitution mutations.
• The approval is supported by findings from the phase 3 MARIPOSA trial (NCT04487080).
• This combination is now the only multitargeted regimen for both common EGFR mutations.

The combination of lazertinib and amivantamab is now FDA-approved for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.^1,2

"This approval is a crucial development for patients with EGFR-mutated NSCLC, who have faced significant unmet needs for far too long," said Jill Feldman, lung cancer survivor and co-founder of the EGFR Resisters, a patient advocacy group, in a press release.² "Having witnessed firsthand the remarkable evolution in lung cancer treatment, this profoundly important milestone brings a novel therapeutic approach to patients and their families. I'm thrilled that more patients can now experience the progression-free survival [PFS] benefits seen in the MARIPOSA study."

With this approval, the combination is now the first and only multitargeted, chemotherapy-free combination regimen that has demonstrated superiority over osimertinib (Tagrisso) for first-line treatment of EGFR-mutated NSCLC.

About the Phase 3 MARIPOSA Trial

The approval is supported by the phase 3 MARIPOSA trial. In the randomized, active-controlled, multicenter trial, 1074 patients were treated with amivanatamab plus lazertinib, lazertinib monotherapy, or osimertinib monotherapy.¹ The combination regimen delivered a statistically significant improvement in PFS, the primary end point, 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 with 16.6 months (95% CI, 14.8-18.5) with osimertinib. At the time of the current analysis, overall survival data were immature, but there was no trend toward a detriment observed.

Regarding safety, the most common adverse events occurring in at least 20% of patients were rash, nail toxicity, amivantamab infusion-related reactions, musculoskeletal pain, edema, stomatitis, venous thromboembolic events (VTE), paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. A serious safety signal for VTE was noted 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 with the MARIPOSA study," said Alexander Spira, MD, PhD, FACP, director of Virginia Cancer Specialists Research Institute and study investigator, in a press release.² "Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib. This first-line therapy uses a targeted approach aiming to achieve the best possible patient outcomes while reserving chemotherapy for later stages of treatment when resistance becomes more complex."

REFERENCES:

1. FDA approves lazertinib with amivantamab-vmjw for non-small lung cancer. News release. FDA. August 19, 2024. Accessed August 20, 2024. https://tinyurl.com/4nnytykz

2. 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://tinyurl.com/2h243n8a