Phase 3 Mariposa study evaluating Rybrevant plus Lazertinib meets primary endpoint in PFS in Non-Small Cell Lung Cancer: Janssen

The pivotal Phase 3 MARIPOSA study met its primary endpoint with a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients receiving RYBREVANT plus lazertinib compared to osimertinib. The combination of RYBREVANT and lazertinib demonstrated a safety profile consistent with previously reported data on the combination. A planned interim overall survival (OS) analysis showed a trend favoring the combination of RYBREVANT and lazertinib compared to osimertinib. Patients in the study will be followed for subsequent OS analyses, which will determine the statistical and clinical significance of OS.

“Positive topline results from the MARIPOSA study reinforce the potential of the RYBREVANT and lazertinib combination in frontline EGFR-mutated non-small cell lung cancer as a future standard of care,” said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “As a combination targeted regimen, RYBREVANT and lazertinib inhibit critical oncogenic driver pathways and activate the immune system to address disease in multiple ways.”

“Patients with treatment-naïve EGFR-mutated non-small cell lung cancer have historically been treated with EGFR TKIs, but these agents invariably lead to resistance and disease progression when used as monotherapy,” said Alexander Spira^†, M.D., Ph.D., FACP, Director, Virginia Cancer Specialists Research Institute, and study investigator. “These promising data from MARIPOSA underscore the potential for the RYBREVANT and lazertinib regimen to advance treatment beyond TKI monotherapy.”

MARIPOSA, which enrolled 1,074 patients, is a randomized, open-label Phase 3 study evaluating RYBREVANT in combination with lazertinib versus osimertinib and versus lazertinib alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions (ex19del) or substitution mutations. The primary endpoint of the study is PFS (using RECIST v1.1 guidelines^‡) as assessed by blinded independent central review. Secondary endpoints include OS, objective response rate (ORR), duration of response (DoR), intracranial PFS, PFS after first subsequent therapy (PFS2) and time to symptomatic progression.

MARIPOSA marks the third RYBREVANT Phase 3 study to readout this year following PAPILLON and MARIPOSA-2. Janssen plans to submit these results for presentation at an upcoming scientific congress, including additional details on select secondary endpoints.