Amivantamab Plus Lazertinib Improves OS in EGFR-Mutant Advanced NSCLC

NSCLC | Image Credit: © Axel Kock

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The combination of amivantamab-vmjw (Rybrevant) and lazertinib (Lazcluze) demonstrated a clinically meaningful and statistically significant improvement in overall survival (OS) vs osimertinib (Tagrisso) alone as first-line therapy for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or L858R substitution mutations, meeting the final prespecified secondary end point of the phase 3 MARIPOSA trial (NCT04487080).¹

The safety profile of the regimen was similar to that of each agent alone, as well as other amivantamab-based regimens. Venous thromboembolic events occurred but were mitigated with subsequent implementation of oral anticoagulant prophylaxis during the initial 4 months of treatment. The survival data will be presented at an upcoming medical meeting and shared with global health authorities.

“The combination of these 2 agents previously demonstrated an improvement in progression-free survival [PFS], but this does not always capture the impact on the entire treatment course. Evaluation of OS can better demonstrate the benefit of a first-line treatment regimen,” 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, stated in a news release. “Seeing this increase in OS in a trial with mature data is powerful and reaffirms that first-line treatment with [amivantamab] and [lazertinib] can lead to better patient outcomes.”

In 2024, the FDA and European Commission approved the combination of amivantamab and lazertinib as frontline treatment for patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.^2,3

Both approvals were based on earlier data from the randomized MARIPOSA trial, which enrolled 1074 patients with newly diagnosed EGFR-mutated NSCLC. The primary end point was PFS per RECIST 1.1 criteria as assessed by blinded independent central review. Secondary end points included OS, objective response rate, duration of response, time to second progression, and intracranial PFS.

Positive topline findings from the interim analysis of the trial, previously presented at the 2023 ESMO Congress, demonstrated that the combination led to a significant improvement in PFS vs osimertinib alone, meeting the primary end point of the study (HR, 0.70; 95% CI, 0.58-0.85; P < .001).^4,5 Additionally, a favorable trend suggestive of OS benefit was seen with the combination (HR, 0.80; 95% CI, 0.61-1.05; P = .11).

“Every milestone in clinical trials and every approval of a new drug or regimen brings hope and progress for [patients with] EGFR-positive [NSCLC] and their families, Marcia Horn, president of International Cancer Advocacy Network, added.¹ “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.”

Updated findings presented at the 2024 IASLC World Conference on Lung Cancer continued to illustrate the earlier trend toward improvement in OS seen with the combination vs osimertinib alone (HR, 0.77; 95% CI, 0.61-0.96; P = .019).⁶

“These new findings reinforce the clinically meaningful impact this chemotherapy-free regimen can have for patients worldwide with NSCLC and represent the first OS benefit over the current standard of care, Yusri Elsayed, MD, MHSc, PhD, Global Therapeutic Area Head, Oncology, Johnson & Johnson Innovative Medicine, stated. “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 OS 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, 2024. Accessed January 7, 2025. https://www.investor.jnj.com/news/news-details/2025/RYBREVANT-amivantamab-vmjw-plus-LAZCLUZE-lazertinib-show-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-versus-osimertinib/default.aspx
2. FDA approves lazertinib with amivantamab-vmjw for non-small cell lung cancer. FDA. August 20, 2024. Accessed January 7, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lazertinib-amivantamab-vmjw-non-small-lung-cancer
3. European Commission approves Rybrevant (amivantamab) in combination with Lazcluze (lazertinib) for the first-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer. News release. Johnson & Johnson. December 30, 2024. Accessed January 7, 2025. https://www.jnj.com/media-center/press-releases/european-commission-approves-rybrevant-amivantamab-in-combination-with-lazcluze-lazertinib-for-the-first-line-treatment-of-patients-with-egfr-mutated-advanced-non-small-cell-lung-cancer
4. Landmark phase 3 MARIPOSA study meets primary end point resulting in statistically significant and clinically meaningful improvement in progression-free survival for Rybrevant (amivantamab-vmjw) plus lazertinib versus osimertinib in patients with EGFR-mutated non-small cell lung cancer. News release. Johnson & Johnson. September 28, 2023. Accessed January 7, 2025. https://www.jnj.com/media-center/press-releases/landmark-phase-3-mariposa-study-meets-primary-endpoint-resulting-in-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-for-rybrevant-amivantamab-vmjw-plus-lazertinib-versus-osimertinib-in-patients-with-egfr-mutated-non-small-cell-lung-cancer
5. Cho BC, Felip E, Spira AI, et al. Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): primary results from MARIPOSA, a phase III, global, randomized, controlled trial. Ann Oncol. 2023;34(suppl 2):S1306. doi:10.1016/j.annonc.2023.10.062
6. Gadgeel S, Cho BC, Lu S, et al. Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced NSCLC: longer follow-up of the MARIPOSA study. Presented at: IASLC 2024 World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. Abstract OA02.03.