Johnson & Johnson (J&J) has announced positive topline results from the Phase 3 MARIPOSA study, revealing that the combination of RYBREVANT® (amivantamab-vmjw) and LAZCLUZE™ (lazertinib) significantly improves overall survival (OS) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations. The study demonstrated a clinically meaningful and statistically significant improvement in OS compared to osimertinib, the current standard of care.
MARIPOSA Trial Results
The MARIPOSA trial, a randomized Phase 3 study, enrolled 1,074 patients to evaluate RYBREVANT in combination with LAZCLUZE versus osimertinib as a first-line treatment. The primary endpoint was progression-free survival (PFS), while secondary endpoints included OS, objective response rate (ORR), duration of response (DOR), and intracranial PFS.
The results indicated that the chemotherapy-free combination regimen met the final pre-specified secondary endpoint of OS, with an expected improvement in median OS exceeding one year. This marks the first regimen to demonstrate a survival benefit over the current standard of care in first-line treatment of EGFR-mutated lung cancer.
Stephen Liu, M.D., Associate Professor of Medicine at Georgetown University School of Medicine and Director of Thoracic Oncology at Georgetown's Lombardi Comprehensive Cancer Center, noted, "Seeing this increase in overall survival in a trial with mature data is powerful and reaffirms that first-line treatment with RYBREVANT and LAZCLUZE can lead to better patient outcomes."
Safety and Tolerability
The safety profile of RYBREVANT plus LAZCLUZE was generally consistent with the known profiles of the individual treatments. While venous thromboembolic events were observed, subsequent studies showed that administering oral anticoagulant medicines prophylactically during the initial four months of the regimen significantly reduced the risk of thrombosis.
Regulatory Status and Clinical Impact
RYBREVANT combined with LAZCLUZE is approved in the United States and Europe for the first-line treatment of patients with EGFR-mutated NSCLC based on the MARIPOSA Phase 3 study. The detailed OS results will be presented at an upcoming major medical meeting and shared with global health authorities.
Yusri Elsayed, M.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson Innovative Medicine, stated, "These MARIPOSA results show RYBREVANT plus LAZCLUZE 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 overall survival by more than a year could be transformative for these patients."
About RYBREVANT and LAZCLUZE
RYBREVANT (amivantamab-vmjw) is a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity. It is approved as monotherapy for NSCLC with EGFR exon 20 insertion mutations and in combination with chemotherapy for first-line treatment of NSCLC with EGFR exon 20 insertion mutations.
LAZCLUZE (lazertinib) is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR.
