MARIPOSA Final OS Results in Asia Population Yield Meaningful Improvement in EGFR NSCLC

In the amivantamab/lazertinib arm, the median OS in the Asian population was not reached vs 38.4 months in the osimertinib arm for patients with EGFR-mutated NSCLC.

A clinically meaningful improvement in overall survival (OS) with amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) was highlighted in the Asian population of the phase 3 MARIPOSA trial (NCT04487080) for patients with locally advanced or metastatic non–small cell lung cancer with EGFR exon 19 deletions or L858R substitution mutations. The final OS results were presented at the European Society for Medical Oncology (ESMO) Asian Congress 2025.1

At a median follow-up of 38.7 months, the median OS was not reached (NR) in the amivantamab plus lazertinib arm compared with 38.4 months (95% CI, 35.1-NR) in the osimertinib (Tagrisso) arm (HR, 0.74; 95% CI, 0.56-0.97; P = .026).2 The 24-month OS rate was 78% vs 74%, the 36-month OS rate was 61% vs 53%, and the 42-month OS rate was 59% vs 46% between the amivantamab/lazertinib and osimertinib arms, respectively.

“Amivantamab plus lazertinib demonstrated a 26% lower risk of death compared with osimertinib monotherapy and is projected to extend survival well beyond what has historically been possible,” said presenting author and lead trial investigator Hidetoshi Hayashi, MD, PhD, professor and senior staff in the Department of Medical Oncology at Kindai University Faculty of Medicine in Osaka-Sakai, Japan. “For patients in Asia, where EGFR-mutated disease is highly prevalent, these findings establish the combination as an important new treatment that advances the standard of care in the first-line setting.”

In the MARIPOSA trial, 501 patients self-identified as Asian.2 The median age was 63 years in the combination arm vs 63 years in the monotherapy arm, 94% vs 95% of patients weighed less than 80 kg, 61% vs 57% of patients were female, and 72% vs 67% had an ECOG performance status of 1. Additionally, 55% vs 55% had an exon 19 deletion, and 45% vs 45% had an L858R mutation.

Previously reported results from MARIPOSA noted that 1074 patients were enrolled and randomly assigned in a 2:2:1 ratio to receive either amivantamab plus lazertinib, osimertinib monotherapy, or lazertinib monotherapy.3 Dosing included 1500 mg of amivantamab or 1400 mg if patients weighed more than 80 kg, given once weekly during the first 28-day cycle, with infusions split over 2 days, followed by every 2 weeks from cycle 2 onward. Lazertinib was given at 240 mg orally daily, and osimertinib was given at 80 mg daily.

At the 2025 European Lung Cancer Conference, the median intracranial progression-free survival was 25.4 months (95% CI, 20.1-29.5) in the combination arm vs 22.2 months (95% CI, 18.4-26.9) in the osimertinib arm (HR, 0.79; 95% CI, 0.61-1.02; P = .07).4

The press release highlighted that the safety profile was consistent with previously reported MARIPOSA data and prior reports in Asian patients. Of note, most adverse effects (AEs) occurred early and were manageable. For Asian patients, the most common grade 3 or higher AEs were rash (18%), dermatitis acneiform (9%), and paronychia (9%). The press releases also highlighted that additional studies have been conducted and found that preventative measures set in place could reduce skin reactions, infusion-related reactions, and venous thromboembolic events.

“These results give real proof that progress is being made for people living with EGFR-mutated lung cancer,” said Kazuo Hasegawa, founder of Lung Cancer Patients Network ONE STEP.1 “For patients and families across Asia, where this disease is especially common, seeing survival extend beyond what once seemed possible brings hope for a different future.”

In August 2024, the FDA approved the combination of amivantamab plus lazertinib.5 Additionally, it is also approved in Europe and the Asia-Pacific region of Japan, China, Australia, Korea, and Taiwan.

References

1. RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE® (lazertinib) delivers statistically significant and clinically meaningful improvement in overall survival benefit for Asian patients with EGFR-mutated non-small cell lung cancer in the phase 3 MARIPOSA study. News release. Johnson & Johnson. December 7, 2025. Accessed December 8, 2025. https://tinyurl.com/4a45w84v
2. @DrJNaidoo. #ESMOAsia2025 Lung Orals🔥MARIPOSA: Asian subgroup analysis @rinrin_1969 - HR OS 0.74 - majority of MARIPOSA made up of asian subset - similar tox signal, & crossing of curves at 9m #ESMOAmbassadors @myesmo @OncoAlert #LCSM. December 7, 2025. Accessed December 8, 2025. https://tinyurl.com/32ebrdbz
3. Asia cohort of phase 3 MARIPOSA study shows RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE® (lazertinib) achieved statistically significant and clinically meaningful improvement in overall survival versus osimertinib in EGFR-mutated non-small cell lung cancer. News release. Johnson & Johnson. September 12, 2025. Accessed December 8, 2025. https://tinyurl.com/2k7teawa
4. Yang JCH, Kim YJ, Lee SH, et al. Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced NSCLC. Presented at the European Lung Cancer Congress 2025; Paris, France; March 26-29, 2025. Abstract 4O.
5. RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) approved in the U.S. as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. August 20, 2024. Accessed December 8, 2025. https://tinyurl.com/yxc8u8t4