Amivantamab Plus Lazertinib Yields OS Advantage in Asia Cohort of MARIPOSA Trial in EGFR-Mutated NSCLC

The first-line combination of amivantamab-vmjw (Rybrevant) and lazertinib (Lazcluze) generated a statistically significant and clinically meaningful overall survival (OS) improvement compared with osimertinib (Tagrisso) in patients with non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or L858R substitution mutations in the Asia cohort of the phase 3 MARIPOSA trial (NCT04487080), meeting the cohort’s final prespecified secondary OS end point.1

The median OS improvement with amivantamab plus lazertinib vs osimertinib is expected to surpass 4 years and exceed by 1 year the median OS historically seen with osimertinib monotherapy.

These data are expected to be reported at a future medical meeting.

Notably, the estimated prevalence of EGFR mutations in Asia is higher than that in Europe and the US, at 30% to 40% vs 10% to 15%, respectively.

“EGFR-mutated NSCLC is more common in Asia Pacific than in other regions, which makes outcomes from the first treatment especially important,” Byoung Chul Cho, MD, PhD, a professor in the Division of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine, in Korea, stated in a news release. “Because of rapid disease progression and health system challenges, many patients will not have the chance to receive a second-line therapy. Therefore, the first treatment determines how the disease progresses over time. The MARIPOSA Asia cohort results show that survival can be significantly extended with amivantamab plus lazertinib in patients of Asian descent, helping them live longer.”

What Was the Design of the MARIPOSA Trial?

The randomized MARIPOSA trial enrolled 1074 patients with newly diagnosed, histologically or cytologically confirmed, locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations.1,2 Patients needed to have treatment-naive disease that was not amenable to curative therapy and had at least 1 measurable lesion.2

Patients in the amivantamab/lazertinib arm received amivantamab at 1050 mg intravenously (IV) for body weight less than 80 kg and 1400 mg IV for body weight of at least 80 kg using a split-dose schedule over 28-day cycles, plus lazertinib at 240 mg orally once daily. Patients in the osimertinib monotherapy arm received osimertinib at 80 mg orally once daily plus a placebo of lazertinib.

Progression-free survival (PFS) served as the primary end point. Key secondary end points included OS, overall response rate (ORR), duration of response (DOR), time to second progression, and intracranial PFS.

What Were the Key Findings From the Total Population in the MARIPOSA Trial?

Among patients who received amivantamab plus lazertinib (n = 429), the median PFS was 23.7 months (95% CI, 19.1-27.7) vs 16.6 months (95% CI, 14.8-18.5) among those who received osimertinib (n = 429; HR, 0.70; 95% CI, 0.58-0.85; P = .0002).3 The median OS in these respective arms was not reached (NR; 95% CI, 42.9 months-not estimable [NE]) vs 36.7 months (95% CI, 33.4-41.0; HR, 0.75; 95% CI, 0.61-0.92; P = .0048). In the amivantamab/lazertinib arm, the ORR was 78% (95% CI, 74%-82%) and included complete (5.4%) and partial (73%) responses. In the osimertinib arm, these respective rates were 73% (95% CI, 69%-78%), 3.5%, and 70%. The median DOR was 25.8 months (95% CI, 20.1-NE) in the amivantamab/lazertinib arm vs 16.7 months (95% CI, 14.8-18.5) in the osimertinib arm.

“For patients and families, every additional year means more time together and the chance to reach milestones that once felt out of reach,” Kazuo Hasegawa, founder of Lung Cancer Patients Network ONE STEP, added in the news release.1 “The MARIPOSA Asia cohort results matter because they show that extending survival is possible in a disease where progress has often been measured in months.”

The safety profile of amivantamab plus lazertinib in the Asia cohort of the study was consistent with that reported in the primary analysis, and no new safety signals were observed with longer follow-up, according to the news release.1

Where Is Amivantamab Plus Lazertinib Approved for the First-Line Treatment of Patients With EGFR-Mutated NSCLC?

In August 2024, the FDA approved frontline amivantamab plus lazertinib for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.4 In January 2025, the European Commission approved amivantamab plus lazertinib for the frontline treatment of adult patients with advanced NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations.5 The combination is also approved for this indication in Canada, Japan, China, Australia, Korea, and Taiwan.1,6 These regulatory decisions were backed by data from MARIPOSA.

“OS is the most meaningful measure of progress, and the MARIPOSA Asia cohort results reinforce the role of therapeutic innovations like amivantamab plus lazertinib in the first-line setting,” Anthony Elgamal, vice president of Oncology at Johnson & Johnson Innovative Medicine Asia Pacific, concluded in the news release.1 “With its triple mode of action targeting EGFR and MET while also activating immune cells, amivantamab plus lazertinib addresses resistance that often limits TKI [tyrosine kinase inhibitor]–based therapy and delivers durable survival. These findings…mark an important milestone for patients across Asia.”

References

1. 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 September 12, 2025. https://www.jnj.com/media-center/press-releases/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
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 August 19, 2025. Accessed September 12, 2025. https://clinicaltrials.gov/study/NCT04487080
3. Rybrevant. Prescribing information. Johnson & Johnson; 2025. Accessed September 12, 2025. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT-pi.pdf
4. FDA approves lazertinib with amivantamab-vmjw for non-small lung cancer. FDA. Updated August 20, 2024. Accessed September 12, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lazertinib-amivantamab-vmjw-non-small-lung-cancer
5. European Commission approves Lazcluze (lazertinib) in combination with Rybrevant (amivantamab) for the first-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer. News release. Johnson & Johnson. January 21, 2025. Accessed September 12, 2025. https://www.jnj.com/media-center/press-releases/european-commission-approves-lazcluze-lazertinib-in-combination-with-rybrevant-amivantamab-for-the-first-line-treatment-of-patients-with-egfr-mutated-advanced-non-small-cell-lung-cancer
6. Health Canada authorizes Lazcluze (lazertinib) in combination with Rybrevant (amivantamab) as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. March 10, 2025. Accessed September 12, 2025. https://innovativemedicine.jnj.com/canada/canada-news-centre/health-canada-authorizes-lazcluze-lazertinib-in-combination-with-rybrevant-amivantamab-as-a-first-line-chemotherapy-free-treatment-for-patients-with-egfr-mutated-advanced-lung-cancer