Topline results from MARIPOSA reveal a survival advantage with amivantamab plus lazertinib vs osimertinib in patients with EGFR-mutant non–small cell lung cancer. Additional follow-up is planned.
Treatment with the EGFR tyrosine kinase inhibitor (TKI) combination of amivantamab-vmj (Rybrevant) and lazertinib (Leclaza) has demonstrated 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).1
The PFS advantage of amivantamab/lazertinib was shown at the topline analysis of the phase 3 MARIPOSA clinical trial (NCT04487080). Results also showed a trend toward overall survival (OS) improvement with amivantamab and lazertinib vs osimertinib. For safety, the profile of amivantamab/lazertinib was consistent with prior data.
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.
"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, in a press release. "These promising data from MARIPOSA underscore the potential for the [amivantamab] and lazertinib regimen to advance treatment beyond TKI monotherapy."
A total of 1074 patients with locally advanced or metastatic EGFR-mutated NSCLC were enrolled in the MARIPOSA study.1,2 Patients were adults aged 18 years or older with histological or cytologically confirmed disease, tissue available for biopsy, at least 1 measurable lesion, and in whom any prior toxicities had be resolved to a grade 1 or lower. Patients were randomized to receive intravenous amivantamab 1050 mg if their body weight is < 80kg or 1400 mg if their body weight is > 80 kg in combination with oral lazertinib 240 mg, in the experimental arm. In the comparator arm, patients received oral osimertinib 80 mg. In another experimental arm, patients receive oral lazertinib 240 mg plus matching placebo and oral osimertinib 80 mg.2
The patients enrolled are being evaluated for the primary end point of PFS, as well as secondary outcomes. The secondary efficacy end points of the study include OS, objective response rate, duration of response, PFS after first subsequent therapy, time to symptomatic progression, and intracranial PFS.
The secondary safety end points of the study include the incidence and severity of adverse events, the number of patients who experience clinical laboratory abnormalities, the number of patients who experience vital sign abnormalities, the number of patients who experience physical examination abnormalities, and the number of patients with anti-amivantamab antibodies. Other secondary end points being assessed include serum concentration of amivantamab, plasma concentration of lazertinib, change from baseline in NSCLC Symptom Assessment Questionnaire, and change from baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30.
"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, in a press release.1 "As a combination targeted regimen, [amivantamab] and lazertinib inhibit critical oncogenic driver pathways and activate the immune system to address disease in multiple ways."
Detailed results from MARIPOSA will be submitted for presentation at an upcoming medical meeting, including data from the study’s secondary end points.
1. Landmark phase 3 MARIPOSA study meets primary endpoint resulting in statistically significant and clinically meaningful improvement in progression-free survival for Rybrevant® (amivantamab-vmjw) plus lazertinib versus osimertinib in patients with EGFR-mutated non-small cell lung cancer. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. September 28, 2023. Accessed September 28, 2023. https://tinyurl.com/t8zw2tyr
2. A study of amivantamab and lazertinib combination therapy versus osimertinib in locally advanced or metastatic non-small cell lung cancer (MARIPOSA). ClincalTrials.gov. Updated September 13, 2023. Accessed September 28, 2023. https://tinyurl.com/yuwtdzpk