The longer follow-up data from the landmark Phase 3 MARIPOSA study has been announced which showed first-line treatment with amivantamab-vmjw combined with lazertinib provided consistent benefit across long-term outcomes compared to osimertinib monotherapy in adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations.

The data show a strong and improving overall survival (OS) trend favouring amivantamab-vmjw plus lazertinib at approximately three years of follow-up. These results were presented in a late-breaking oral presentation at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer (WCLC) (Abstract #1146).

At three years (a median follow-up of 31.1 months), 61 percent of patients receiving amivantamab-vmjw plus lazertinib were alive compared to 53 percent of those treated with osimertinib based on an analysis performed at the request of a health authority (Median OS not estimable vs 37.3 months; hazard ratio [HR], 0.77; [95 percent confidence interval [CI], 0.61-0.96]; nominal P=0.019).

Overall survival will continue to be assessed with longer term follow-up as a key secondary endpoint. The primary efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR).

"By combining the multi-targeted mechanism of amivantamab-vmjw with lazertinib, a central nervous system-penetrant third-generation tyrosine kinase inhibitor, we are advancing a chemotherapy-free regimen for the first-line treatment of patients with EGFR-mutant NSCLC. This approach blocks EGFR and MET pathways and leverages the immune system, offering patients an opportunity for prolonged benefits," said Shirish M. Gadgeel, M.D., Chief of Division of Hematology and Oncology, Associate Director at Henry Ford Cancer Institute and presenting author.

"Even more encouraging is the marked improvement in the hazard ratio and the ongoing separation of survival curves, showing an eight percent improvement at three years for amivantamab-vmjw plus lazertinib compared to osimertinib. This supports the long-term benefit of the combination as a first-line treatment option in this setting."

Results further showed amivantamab-vmjw plus lazertinib demonstrated a trend toward improved central nervous system disease control compared to osimertinib at three years (HR, 0.82; [95 percent CI, 0.62-1.09]; nominal P=0.165). At the three-year landmark, intracranial PFS was double for amivantamab-vmjw plus lazertinib versus osimertinib (38 percent vs 18 percent, respectively).

More patients remained on treatment at three years with the amivantamab-vmjw combination compared to osimertinib (40 percent vs 29 percent, respectively; HR, 0.80; [95 percent CI, 0.68-0.96]; nominal P=0.014).

Additionally, more patients receiving amivantamab-vmjw and lazertinib at the three-year follow-up had not started a subsequent therapy versus osimertinib (45 percent vs 32 percent, respectively; HR, 0.77; [95 percent CI, 0.65-0.93]; nominal P=0.005).

Progression-free survival after first subsequent therapy was 57 percent for the amivantamab-vmjw combination compared to 49 percent for osimertinib (HR, 0.73; [95 percent CI, 0.59-0.91]; nominal P=0.004).

"Promising results like these presented at WCLC reinforce our mission to improve the lives of patients diagnosed with lung cancer," said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine.

"We are encouraged by the favourable overall survival trend observed with amivantamab-vmjw plus lazertinib and are eager to see how these data evolve as we continue to follow patients over time." 

As previously reported in the MARIPOSA study, the safety profile was consistent with the safety profiles of the individual treatments.

The rate of discontinuation of all study treatments due to treatment-related adverse events for amivantamab-vmjw plus lazertinib was 10 percent. The rate of interstitial lung disease (including pneumonitis) was less than three percent in both arms.

In August 2024, amivantamab-vmjw combined with lazertinib was approved following a Priority Review by the U.S. Food and Drug Administration as a first-line therapy for patients with EGFR-mutated NSCLC based on the favourable efficacy and safety profile demonstrated in this study.

Source: Johnson&Johnson