The amivantamab plus lazertinib combination regimen offers potential to provide new standard of care as first-line option for adult patients with advanced NSCLC with EGFR ex19del or L858R substitution mutations. In the Phase 3 MARIPOSA study, amivantamab plus lazertinib significantly reduced risk of disease progression or death by 30 percent versus osimertinib monotherapy.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the Marketing Authorisation 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 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 3 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).1 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 1-2 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. 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) and dermatitis
acneiform (8 percent).

1 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 less than three percent in both arms.

“These CHMP positive opinions mark a pivotal step in our mission to deliver transformative first-line therapies for people living with EGFR-mutated NSCLC,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumours, Johnson & Johnson Innovative Medicine. “Based on the growing body of promising results we’ve seen to date and our ongoing clinical development programme, we believe amivantamab has the potential to become a foundational therapy for EGFR-and MET-driven NSCLC.”

Source: Johnson & Johnson