Rybrevant, Lazcluze Combination Demonstrates Improvement in Patients with Advanced Non-Small Cell Lung Cancer

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Results from the Phase III MARIPOSA trial demonstrated improved outcomes with Johnson & Johnson’s (J&J) Rybrevant (amivantamab-vmjw) combined with Lazcluze (lazertinib) compared to osimertinib in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Data from the study show that at three years of follow-up, the combination treatment demonstrated a strong overall survival (OS) rate.¹

“By combining the multi-targeted mechanism of Rybrevant with Lazcluze, 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 presenting author Shirish M. Gadgeel, MD, chief, division of hematology and oncology, associate director, Henry Ford Cancer Institute, in a press release. “Even more encouraging is the marked improvement in the hazard ratio and the ongoing separation of survival curves, showing an 8% improvement at three years for Rybrevant plus Lazcluze compared to osimertinib. This supports the long-term benefit of the combination as a first-line treatment option in this setting.”

The randomized MARIPOSA trial evaluated the combination of Rybrevant and Lazcluze against Lazcluze alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations. Consisting of 1,074 patients, the primary endpoint of the study was progression-free survival (PFS) as assessed by blinded independent central review (BICR).

Results found that at three years of follow-up, the combination therapy produced an 8% improvement in OS compared to osimertinib, with 61% of patients alive versus 53% for osimertinib. Additionally, the combination therapy was found superior in improving central nervous system disease control compared to osimertinib at three years, with data showing a 38% improvement rate compared to 18% for Osimertinib; however, median OS was not estimable for the combination.

The safety profile of Rybrevant and Lazcluze was consistent with previous studies of both treatments on their own. J&J started that discontinuation due to treatment-related adverse events (AEs) occurred in 10% of patients.

Common AEs included rash, nail toxicity, infusion-related reactions, musculoskeletal pain, stomatitis, edema, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritis, nausea, and ocular toxicity. Common grade 3 or 4 laboratory abnormalities included decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, and increased magnesium. Serious AEs were reported in 49% of patients who received the combination treatment.¹

According to American Cancer Society statistics, anywhere from 80% to 85% of all lung cancers are NSCLC. It is estimated that by the end of this year, there will be 234,580 cases of newly diagnosed lung cancer in the United States, with 125,070 deaths. While it mainly occurs in older people, a small number of individuals have been diagnosed under the age of 45 years. Currently, lung cancer is the leading cause of cancer deaths in the United States.²

“Promising results like these presented at WCLC reinforce our mission to improve the lives of patients diagnosed with lung cancer,” said Joshua Bauml, MD, VP, lung cancer disease area stronghold leader, Johnson & Johnson Innovative Medicine, in the press release. “We are encouraged by the favorable overall survival trend observed with Rybrevant plus Lazcluze and are eager to see how these data evolve as we continue to follow patients over time.”

References

1. RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) show strong favorable overall survival trend versus osimertinib in EGFR-mutated advanced lung cancer. Janssen. September 8, 2024. Accessed September 9, 2024. https://www.janssen.com/rybrevantr-amivantamab-vmjw-plus-lazcluzetm-lazertinib-show-strong-favorable-overall-survival-trend

2. Key Statistics for Lung Cancer. American Cancer Society. Accessed September 9, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html