Amivantamab Combo Significantly Improves OS in Asian EGFR+ NSCLC Population

Full overall survival results with amivantamab plus lazertinib from the Asia cohort of the MARIPOSA trial will be shared at a future medical conference.

Frontline amivantamab (Ryebrevant) plus lazertinib (Lazcluze) demonstrated a clinically meaningful and statistically significant survival improvement in Asian patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or L858R substitution mutations in the Asia cohort of the phase 3 MARIPOSA study (NCT04487080), according to a press release from the developer, Johnson & Johnson.¹

The treatment combination met the final pre-specified secondary end point of overall survival (OS) compared with osimertinib (Tagrisso) monotherapy; the median OS is anticipated to exceed 4 years, which will be 1 year higher than what was observed with osimertinib. Complete OS results from the Asia cohort will be shared at an upcoming medical conference. Notably, EGFR mutations are more common in patients from the Asian region compared with patients from other regions.

In all patients, the median OS with the experimental combination was not estimable (NE; 95% CI, 42.9-NE) vs 36.7 months (95% CI, 33.4-41.0) with osimertinib (HR, 0.75; 95% CI, 0.61-0.92; P = .005).² At 3 years, the OS rate was 60% (95% CI, 55%-64%) vs 51% (95% CI, 46%-55%), respectively.

A subgroup analysis of OS showed that results were favorable with amivantamab plus lazertinib in patients who are Asian (HR, 0.75; 95% CI, 0.58-0.98) and not Asian (HR, 0.74; 95% CI, 0.54-1.00).

Previously, in August 2024, the FDA approved the amivantamab plus lazertinib combination as frontline therapy for this EGFR-mutated advanced NSCLC population.³ The combination is also approved in Europe and the Asia-Pacific region of Japan, China, Australia, Korea, and Taiwan. All approvals are based on results from MARIPOSA.

“EGFR-mutated NSCLC is more common in [the] Asia-Pacific [region] than in other regions, which makes outcomes from the first treatment especially important,” Byoung Chul Cho, MD, PhD, professor in the Division of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine, said in the press release.¹ “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.”

MARIPOSA was a randomized trial that evaluated amivantamab in combination with lazertinib compared with osimertinib monotherapy in the first-line treatment of patients with EGFR-mutated NSCLC. A total of 1074 patients were enrolled in the trial and randomly assigned, in a 2:1:1 ratio, to receive either amivantamab plus lazertinib, osimertinib monotherapy, or lazertinib monotherapy.

Patients received 1050 mg of amivantamab intravenously weekly—or 1400 mg in those with a weight of 80 kg or heavier—for the first 4 cycles, with initial infusion split over a period of 2 days, then every 2 weeks from cycle 2 onward. Lazertinib was administered orally at 240 mg daily, and osimertinib was administered orally at 80 mg daily.

Eligible patients were 18 years or older and had previously untreated EGFR-mutated locally advanced or metastatic NSCLC. Those with asymptomatic or previously treated and stable brain metastases were permitted entry.

The trial’s primary end point was progression-free survival (PFS) per RECIST v1.1 criteria, assessed by blinded independent central review. A key secondary end point was OS; other secondary end points were objective response rate, duration of response, intracranial PFS, and PFS2.

Regarding safety, amivantamab and lazertinib showed consistent profiles with what has been previously observed in the primary analysis, with no new safety signals emerging at the longer follow-up.

At least 1 adverse event (AE) of grade 3 or higher occurred in 80% of the combination therapy group vs 52% in the osimertinib group. The most common grade 3 AEs in the combination group were rash (17%), paronychia (12%), and dermatitis acneiform (9%).

“For patients and families, every additional year means more time together and the chance to reach milestones that once felt out of reach,” stated Kazuo Hasegawa, the founder of Lung Cancer Patients Network ONE STEP, in the press 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.”

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://tinyurl.com/2k7teawa
2. Yang JC, Lu S, Hayashi H, et al. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. Published online September 7, 2025. doi:10.1056/NEJMoa2503001
3. 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 September 12, 2025. https://tinyurl.com/yxc8u8t4