The combination of amivantamab (Rybrevant) and lazertinib (Leclaza) has demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with osimertinib (Tagrisso) in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC). This was shown in the topline analysis of the phase 3 MARIPOSA clinical trial (NCT04487080).
Results from the MARIPOSA trial also indicated a trend toward overall survival (OS) improvement with amivantamab and lazertinib versus osimertinib. The safety profile of the combination was consistent with prior data.
MARIPOSA Trial Details
The MARIPOSA study enrolled 1074 patients with locally advanced or metastatic EGFR-mutated NSCLC. Patients were adults aged 18 years or older with histologically or cytologically confirmed disease, tissue available for biopsy, at least 1 measurable lesion, and in whom any prior toxicities had resolved to a grade 1 or lower. Patients were randomized to receive intravenous amivantamab at 1050 mg (if body weight < 80kg) or 1400 mg (if body weight > 80 kg) in combination with oral lazertinib 240 mg, in one experimental arm. In the comparator arm, patients received oral osimertinib 80 mg. Another experimental arm received oral lazertinib 240 mg plus placebo and oral osimertinib 80 mg.
The primary endpoint of the study was PFS, with secondary endpoints including OS, objective response rate, duration of response, PFS after first subsequent therapy, time to symptomatic progression, and intracranial PFS. Safety endpoints included the incidence and severity of adverse events, clinical laboratory abnormalities, vital sign abnormalities, physical examination abnormalities, and the presence of anti-amivantamab antibodies.
Expert Commentary
"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, MD, PhD, FACP, director, Virginia Cancer Specialists Research Institute, and study investigator. "These promising data from MARIPOSA underscore the potential for the [amivantamab] and lazertinib regimen to advance treatment beyond TKI monotherapy."
Future Directions
Detailed results from MARIPOSA will be submitted for presentation at an upcoming medical meeting, including data from the study’s secondary endpoints. Subsequent OS analyses in MARIPOSA are planned to determine whether OS improvement with amivantamab and lazertinib compared with osimertinib holds any statistical or clinical significance.
"Positive topline results from the MARIPOSA study reinforce the potential of the [amivantamab] and lazertinib combination in frontline EGFR-mutated non–small cell lung cancer as a future standard of care," said Peter Lebowitz, MD, PhD, global therapeutic area head, oncology, Janssen Research & Development, LLC. "As a combination targeted regimen, [amivantamab] and lazertinib inhibit critical oncogenic driver pathways and activate the immune system to address disease in multiple ways."
