Janssen-Cilag International NV, a Johnson & Johnson company, today announced that the European Commission (EC) has approved a Marketing Authorisation (MA) for lazertinib, in combination with amivantamab, for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or exon 21 L858R (L858R) substitution mutations.

The EC approval is supported by results from the Phase 3 MARIPOSA (NCT04487080) study, evaluating lazertinib in combination with amivantamab 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 of progression-free survival (PFS).

These data 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).

On 7 January 2025, J&J announced new positive topline overall survival (OS) results showing that amivantamab plus lazertinib met the final pre-specified secondary endpoint of OS and demonstrated clinically meaningful and statistically significant improvement in OS versus the current standard of care,
osimertinib monotherapy.

Median OS is expected to exceed one year.1 These landmark OS data will be presented at an upcoming medical meeting. “This chemotherapy-free regimen has already demonstrated significant progression-free survival improvements, and new topline data suggests it is expected to extend life by a median of one year or more, in patients with untreated EGFR-mutated NSCLC versus the current standard of care, osimertinib,” said Antonio Passaro*, M.D., Ph.D., medical oncologist of the Division of Thoracic Oncology, European Institute of Oncology in Milan, Italy. “These results mark a significant step forward in the treatment of EGFR-mutated NSCLC. Extending life expectancy is a critical indicator of a treatment’s impact. The MARIPOSA study reaffirms the potential of first-line treatment with this combination therapy to redefine the standard of care and offer clinically meaningful improvements in outcomes for patients.”

Previously reported findings from the MARIPOSA study have shown the safety profile of the combination of amivantamab and lazertinib to be consistent with findings from Phase 1-2 studies, with mostly Grade 1 or 2 adverse events (AEs).2 Toxicity was largely manageable with dose interruptions and reductions, along with supportive care measures commonly used in the treatment of patients with NSCLC.

The most common treatment emergent adverse events (TEAEs) of any grade were paronychia (68 percent), infusion-related reactions (63 percent), and rash (62 percent). Amivantamab plus lazertinib had higher rates of EGFR- and MET-related AEs and venous thromboembolism compared to osimertinib, except diarrhoea, for which rates were higher for osimertinib.

The commonest grade 3 or higher TEAEs were rash (15 percent), paronychia (11 percent), dermatitis acneiform (8 percent) and pulmonary embolism
(8%). The rate of discontinuation of all study treatments due to treatment-related AEs for the amivantamab combination was 10 percent. The rate of interstitial lung disease (including pneumonitis) was three percent in both arms.

“Currently, the five-year survival rate for patients with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors is less than 20 percent,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology. “Today’s approval marks an important moment in lung cancer care, bringing a new option to patients through a chemotherapy-free regimen, and potentially offering more time
with their loved ones.”

This EC decision follows a corresponding EC approval in December 2024 of a Type II variation extension of indication for the bispecific antibody amivantamab, in combination with lazertinib, for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.5

Source: Johnson & Johnson