CHMP recommends Rybrevant (amivantamab) plus Lazcluze (lazertinib) for the first-line treatment of EGFR-mutated advanced non-small cell lung cancer

The CHMP has simultaneously recommended approval of a Type II extension of indication for amivantamab in the same combination regimen.

“Lung cancer remains the leading cause of cancer-related deaths globally, and patients with EGFR-mutated advanced non-small-cell lung cancer are in need of new targeted treatment options,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “Pending European Commission approval, the combination of amivantamab with lazertinib could establish a new first-line standard of care, with the potential to significantly delay disease progression and improve outcomes early in the treatment pathway while reserving chemotherapy regimens for later stages of treatment when resistance becomes more complex.”

The CHMP positive opinions for the MA and Type II extension of indication are supported by data from the Phase III MARIPOSA (NCT04487080) study, evaluating amivantamab in combination with lazertinib compared to osimertinib as first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or exon 21 L858R substitution mutations. The study met its primary endpoint, and at median follow-up of 22 months, reduced the risk of disease progression or death by 30 percent compared to osimertinib (median progression-free survival [PFS]: 23.7 months compared to 16.6 months for osimertinib; hazard ratio [HR]=0.70; 95 percent confidence Interval [CI], 0.58–0.85; P<0.001) as assessed by blinded independent central review (BICR).The median duration of response (DOR) was significantly longer for patients receiving amivantamab plus lazertinib compared to osimertinib, with a nine-month improvement in median DOR (25.8 vs. 16.8 months).

Results from the MARIPOSA study were featured during a Presidential Symposium session at the 2023 European Society of Medical Oncology (ESMO) Congress, with longer-term follow-up data presented at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer (WCLC). The MARIPOSA study required all patients to have serial brain imaging with magnetic resonance imaging (MRI) in order to detect or monitor brain metastases, a measure not implemented in most prior studies for EGFR-mutated NSCLC  The primary endpoint of PFS in MARIPOSA included these central nervous system (CNS) events detected by serial brain MRIs.  The median PFS when censoring CNS-only first progressions was 27.5 months for the combination of amivantamab and lazertinib, compared to 18.4 months for osimertinib (HR=0.68; 95 percent CI, 0.55–0.83; P<0.001).

Longer-term follow-up data shows a strong favourable overall survival trend for amivantamab plus lazertinib versus osimertinib. At three years (median follow-up of 31.1 months), 61 percent of patients receiving amivantamab plus lazertinib were alive compared to 53 percent of those treated with osimertinib based on an analysis performed at the request of health authorities (Median OS not estimable [NE] vs 37.3 months; HR=0.77; 95 percent CI, 0.61-0.96; nominal P=0.019).

The safety profile of the combination of amivantamab and lazertinib was consistent with previous reports from Phase 1-II studies, with mostly Grade 1 or 2 adverse events (AEs). Toxicity was largely manageable with dose interruptions and reductions, along with supportive care measures commonly used in the treatment of patients with NSCLC.