J&J Reports Positive Late-Stage Results for Rybrevant/Lazcluze Combo in NSCLC

Johnson & Johnson (J&J) has revealed promising long-term data for its chemotherapy-free combination of Rybrevant (amivantamab-vmjw) and Lazcluze (lazertinib) in adults with non-small cell lung cancer (NSCLC). This announcement follows shortly after the US Food and Drug Administration (FDA) approved the combination as a first-line treatment for NSCLC patients with specific genetic mutations—epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitutions.

The decision by the FDA was influenced by the findings of the phase 3 MARIPOSA trial. This trial assessed the efficacy of the EGFRxMET bispecific antibody, Rybrevant, in combination with the third-generation EGFR tyrosine kinase inhibitor (TKI), Lazcluze. These results were compared against AstraZeneca’s third-generation EGFR-TKI, Tagrisso (osimertinib), in patients with similar genetic profiles.

At the World Conference on Lung Cancer, new data from the MARIPOSA trial disclosed that 61% of patients treated with Rybrevant plus Lazcluze were still alive after a median follow-up period of 31.1 months. This is in contrast to 53% of patients who received Tagrisso. Additionally, the combination demonstrated a tendency towards better control of central nervous system (CNS) disease compared to Tagrisso. Importantly, more patients on the Rybrevant and Lazcluze regimen remained on treatment and had not initiated subsequent therapies at the three-year mark.

The company noted that overall survival will continue to be monitored as a significant secondary endpoint with extended follow-up. This is crucial given that NSCLC represents approximately 85% of all lung cancer cases, with EGFR mutations being a common driver in this disease subset. A significant portion—up to 39%—of patients with EGFR-mutated NSCLC do not receive second-line treatments due to disease progression and limited treatment options. Acquired resistance mechanisms following standard TKI monotherapies further complicate subsequent treatments.

Dr. Shirish Gadgeel from the Henry Ford Cancer Institute, who presented the findings, remarked, “By combining the multi-targeted mechanism of Rybrevant with Lazcluze, a CNS-penetrant third-generation TKI, we are advancing a chemotherapy-free regimen for first-line treatment of patients with EGFR-mutant NSCLC. This strategy blocks both EGFR and MET pathways while engaging the immune system, providing patients with the potential for extended benefits.”

Joshua Bauml, Vice President and leader of the lung cancer disease area at J&J Innovative Medicine, shared the company's optimism regarding the positive overall survival trend observed with this combination treatment. He expressed eagerness to see how the data progresses over time.

The effort to develop a chemotherapy-free approach for treating NSCLC is a significant step forward, particularly for patients with EGFR mutations, who often face limited options post-progression. Combining Rybrevant's multi-targeted approach with Lazcluze’s CNS-penetrant properties may offer a more effective and sustainable treatment pathway, underscoring the potential for innovative therapies in improving patient outcomes in lung cancer.