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

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Lazertinib and amivantamab as a first-line treatment for patients with locally advanced or metastatic non–small cell lung cancer with specific EGFR mutations demonstrated superior efficacy compared with standard treatment.

Lung cancer and lung disease, generative AI: © Royalty-Free - stock.adobe.com

Lung cancer and lung disease, 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 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
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