First-Line Amivantamab Plus Lazertinib Meets PFS End Point in EGFR+ NSCLC

Alexander Spira, MD, PhD, FACP

First-line treatment with the combination of amivantamab-vmjw (Rybrevant) and lazertinib (Leclaza) resulted in a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with osimertinib (Tagrisso) in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR mutations, meeting the primary end point of the phase 3 MARIPOSA trial (NCT04487080).¹

A planned interim analysis showed an overall survival (OS) trend favoring amivantamab plus lazertinib. Additional follow-up and subsequent analyses will be used to determine the significance of the OS data. Moreover, safety findings were consistent with previously reported findings for the combination of amivantamab and lazertinib.

Detailed findings will be presented at an upcoming medical conference, including additional data on secondary end points.

“Patients with treatment-naïve EGFR-mutated NSCLC have historically been treated with EGFR TKIs, but these agents invariably lead to resistance and disease progression when used as monotherapy,” Alexander Spira, MD, PhD, FACP, director of the Virginia Cancer Specialists Research Institute and MARIPOSA study investigator, stated in a news release. “These promising data from MARIPOSA underscore the potential for the [amivantamab] and lazertinib regimen to advance treatment beyond TKI monotherapy.”

The open-label, randomized MARIPOSA trial enrolled 1074 patients who were at least 18 years of age and had newly diagnosed histologically or cytologically confirmed, locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitutions.1,2 Patients were required to have at least 1 measurable lesion per RECIST v1.1 criteria.² 

Key exclusion criteria consisted of having received any prior systemic treatment for locally advanced stage III or metastatic stage IV NSCLC; active or past leptomeningeal disease; untreated spinal cord compression; active or past interstitial lung disease/pneumonitis; and symptomatic brain metastases.

Patients were randomly assigned to 1 of 3 treatment arms. In the first experimental group (arm A), patients received 1050 mg of intravenous (IV) amivantamab (for those with a body weight <80 kg) or 1400 mg of IV amivantamab (for those with a body weight ≥ 80 kg) once weekly in cycle 1 with a split dose on days 1 and 2, followed by once every 2 weeks in subsequent cycles, plus 240 mg of oral lazertinib once per day. In the control group (arm B), patients received 80 mg of oral osimertinib once per day plus a matching lazertinib placebo once per day. In the other experimental group (arm C), patients received 240 mg of lazertinib once per day plus a matching osimertinib placebo once per day.

Notably, only arms B and C were double blinded.

Along with the primary end point of blinded independent central review–assessed PFS per RECIST v1.1 criteria, secondary end points included OS, objective response rate, duration of response, PFS after first subsequent therapy, intracranial PFS, and safety.

“Positive topline results from the MARIPOSA study reinforce the potential of the [amivantamab] and lazertinib combination in frontline EGFR-mutated NSCLC as a future standard of care,” Peter Lebowitz, MD, PhD, global therapeutic area head of oncology at Janssen, stated in a news release. “As a combination targeted regimen, [amivantamab] and lazertinib inhibit critical oncogenic driver pathways and activate the immune system to address disease in multiple ways.”

References

1. Landmark phase 3 MARIPOSA study meets primary endpoint resulting in statistically significant and clinically meaningful improvement in PFS for Rybrevant (amivantamab-vmjw) plus lazertinib versus osimertinib in patients with EGFR-mutated NSCLC. News release. Janssen. September 28, 2023. Accessed September 28, 2023. https://www.janssen.com/landmark-phase-3-mariposa-study-meets-primary-endpoint-resulting-statistically-significant
2. A study of amivantamab and lazertinib combination therapy versus osimertinib in locally advanced or metastatic non-small cell lung cancer (MARIPOSA). ClinicalTrials.gov. Updated September 13, 2023. Accessed September 28, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04487080