Amivantamab and Lazertinib Combo Extends Survival in EGFR+ NSCLC

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The phase 3 MARIPOSA study (NCT04487080) of amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) as a frontline treatment for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or L858R substitution mutations has met its final prespecified secondary end point of overall survival (OS).¹

The combination showed a clinically meaningful and statistically significant OS improvement vs the current standard of care of osimertinib (Tagrisso) in this patient population. The improvement in median OS is expected to exceed 1 year.

These findings, which come from the final OS analysis of the MARIPOSA trial, follow the release of data from the study’s interim analysis and positive results from the progression-free survival (PFS) analysis. Of the 1074 patients enrolled, the median PFS in the amivantamab/lazertinib arm was 23.7 months vs 16.6 months in the osimertinib group (HR, 0.70; 95% CI, 0.58-0.8; P <.001). The overall response rate (ORR) was 86% (95% CI, 83%-89%) vs 85% (95% CI, 81%-88%), respectively, and the median duration of response was 25.8 months (95% CI, 20.1-not estimable [NE]) vs 16.8 months (95% CI, 14.8-18.5), respectively.²

"The combination of these 2 agents previously demonstrated an improvement in progression-free survival, but this does not always capture the impact on the entire treatment course. Evaluation of overall survival can better demonstrate the benefit of a first-line treatment regimen," said Stephen Liu, MD, associate professor of medicine at Georgetown University School of Medicine and director of Thoracic Oncology and Head of Developmental Therapeutics at Georgetown's Lombardi Comprehensive Cancer Center, in a press release.¹ "Seeing this increase in overall survival in a trial with mature data is powerful and reaffirms that first-line treatment with [amivantamab] and [lazertinib] can lead to better patient outcomes."

For safety, the combination of amivantamab plus lazertinib was generally consistent with the profiles of each individual treatment and the adverse event rates were similar in the combination arm with those seen in other regimens with amivantamab.

With the combination, venous thromboembolic events were observed. Furthermore, later studies demonstrated that prophylactic administration of oral anticoagulant medications during the first 4 months of the amivantamab and lazertinib regimen notably decreased the risk of thrombosis.

The OS results will be shared at an upcoming major medical conference and communicated to regulatory health authorities worldwide. The combination therapy has been approved in various regions, including the US and Europe, for the treatment of patients with specific types of advanced cancer, based on pivotal clinical trial results.

"Every milestone in clinical trials and every approval of a new drug or regimen brings hope and progress for EGFR-positive patients and their families," said Marcia Horn, president of International Cancer Advocacy Network, in the press release. "These topline data from the MARIPOSA trial offer renewed optimism in the journey to extend life for EGFR-mutated patients, adding another important option for patients and oncologists."

"These new findings reinforce the clinically meaningful impact this chemotherapy-free regimen can have for patients worldwide with non-small cell lung cancer and represent the first overall survival benefit over the current standard of care," said Yusri Elsayed, MD, MHSc, PhD, global therapeutic area head, oncology, Johnson & Johnson Innovative Medicine, in the press release. "With less than 20 percent of patients living beyond five years, an incredible unmet need remains for EGFR-positive lung cancer. These MARIPOSA results show [amivantamab] plus [lazertinib] can extend survival beyond the current standard of care, providing patients with more time and hope in their fight against this devastating disease. Extending median overall survival by more than a year could be transformative for these patients."

REFERENCES:

1. RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) show statistically significant and clinically meaningful improvement in overall survival versus osimertinib. News release. Johnson & Johnson. January 7, 2025. Accessed January 7, 2025. https://tinyurl.com/2u96jv79

2. Cho B, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med. Published June 26, 2024. doi:10.1056/NEJMoa2403614