Johnson & Johnson has released new findings from the Phase 3 MARIPOSA trial showing that combining RYBREVANT with LAZCLUZE as a first-line treatment significantly lowers the risk of resistance caused by EGFR and MET mutations. This is compared to using osimertinib alone in patients with EGFR-mutated non-small cell lung cancer (NSCLC) who have either exon 19 deletion or L858R mutations. These results support earlier data showing the treatment extends survival beyond four years—about a year longer than osimertinib—demonstrating its potential to change the disease’s progression by preventing acquired resistance. The findings were presented at the 2025 World Congress on Lung Cancer organized by the International Association for the Study of Lung Cancer.
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Resistance to third-generation EGFR tyrosine kinase inhibitors such as osimertinib remains a significant hurdle for long-term disease control. This ongoing challenge highlights the urgent need for new treatment strategies that better prevent resistance in both the EGFR and MET pathways, ultimately improving survival outcomes for patients with EGFR-mutated lung cancer.
Professor Sanjay Popat, a medical oncologist at the Royal Marsden Hospital and the Institute of Cancer Research in the UK, emphasized that current evidence shows monotherapy with TKIs is no longer sufficient as a first-line treatment for EGFR-mutated lung cancer. He described the combination of RYBREVANT and LAZCLUZE as an important advancement that reduces resistance caused by EGFR and MET alterations, providing patients with a longer and more robust initial response.
The updated data from the MARIPOSA trial reinforce previous findings presented at the European Society for Medical Oncology 2024 Congress. They show that patients treated with the combination experienced far fewer instances of MET amplification and secondary EGFR mutations compared to those on osimertinib alone. MET amplifications occurred in only 3 percent of patients on the combination versus 13 percent on osimertinib. Secondary EGFR mutations such as C797S appeared in just 1 percent of the combination group compared to 8 percent in the osimertinib group. Additionally, patients on osimertinib had a higher rate of early treatment discontinuation due to acquired MET amplification within six months. In contrast, those on the combination who continued treatment beyond six months had very low resistance rates, with minimal MET amplifications and no C797S mutations detected. The study also noted greater diversity in resistance mechanisms among osimertinib-treated patients, particularly involving EGFR and MET changes.
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Joshua Bauml, M.D., Vice President and Lung Cancer Disease Area Leader at Johnson & Johnson Innovative Medicine, highlighted the critical role of selecting the appropriate first-line therapy for EGFR-mutated NSCLC. He explained that the choice impacts disease progression and long-term patient outcomes. According to him, the data show that RYBREVANT and LAZCLUZE work together to block the common resistance pathways cancers use, extending survival and keeping future treatment options open. He added that these benefits have not been observed with previous therapies or other combinations currently under investigation. The safety profile of RYBREVANT and LAZCLUZE remains consistent with earlier reports, with most serious side effects occurring early in treatment. Studies suggest that proactive management of side effects such as skin reactions, infusion-related reactions, and blood clots can reduce their severity. RYBREVANT and LAZCLUZE are approved in the United States, Europe, and other regions for first-line treatment of EGFR-mutated NSCLC based on the MARIPOSA trial.
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