CHMP Recommends Lazertinib With Amivantamab to Treat EGFR-Mutated Advanced NSCLC

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the Marketing Authorization (MA) for lazertinib (Lazcluze; Janssen Biotech Inc) in combination with amivantamab (Rybrevant; Janssen Biotech Inc). The drug is aimed to treat individuals 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. An additional approval of a type II extension of indication for amivantamab to treat the same patient population was also recommended.¹

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Lung cancer remains the leading cause of cancer death globally, with around 2.4 million new cases and 1.8 million deaths in 2022.² However, in Europe specifically, an estimated 484,306 individuals were diagnosed with lung cancer in 2022, as NSCLC accounted for 85% of cancer cases, according to study authors.¹

"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," Henar Hevia, PhD, senior director and EMEA therapeutic area lead of Oncology at Johnson & Johnson Innovative Medicine, said in the press release.¹

EGFR is a receptor tyrosine kinase that controls cell growth and division, and its alterations are the most common driver mutations in NCSLC. The most common EGFR mutations are EGFR ex19del or EGFR exon 21 L858R, with a less than 20% 5-year survival rate among individuals treated with EGRF TKIs. Additionally, the study authors noted 25% to 32% of individuals treated with osimertinib—the current first-line standard of care—do not survive long enough to receive second line treatment.¹

As a fully human EGRF-MET bispecific antibody, amivantamab acts by targeting tumors with activating and resistance EGFR mutations and MET mutations and amplifications, along with binding the immune system. The combination drug, lazertinib is an oral, third-generation, brain-penetrant EGRF TKI that works by targeting the T790M mutation and activating EGFR mutations, but sparing wild-type EGFR, according to study authors.¹

“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,” Hevia said in the press release.¹

The MA and type II extension was granted based on the phase 3 MARIPOSA study (NCT04487080), that assessed amivantamab combined with lazertinib with osimertinib as the first line of treatment for individuals with advanced or metastatic NSCLC with EGFR ex19del or exon 21 L858R substitution mutations. The results displayed positive outcomes, meeting the primary endpoint of progression free survival. The combination drug reduced the risk of disease progression or death by 30% compared with osimertinib. Amivantamab plus lazertinib also had a 9-month improvement in median duration of response, which was significantly longer than treatment with osimertinib.¹

“These CHMP positive opinions mark a pivotal step in our mission to deliver transformative first-line therapies for people living with EGFR-mutated NSCLC,” Kiran Patel, MD, vice president of clinical development of solid tumors at Johnson & Johnson Innovative Medicine, said in the press release.¹

The safety profile of amivantamab plus lazertinib included mostly grade 1 or grade 2 adverse events. Treatment emergent adverse reactions included paronychia, infusion-related reactions, and rash. However, rash, paronychia, and dermatitis acneiform were the most common grade or higher treatment emergent adverse reactions.¹

“Based on the growing body of promising results we’ve seen to date and our ongoing clinical development programmed, we believe amivantamab has the potential to become a foundational therapy for EGFR- and MET-driven NSCLC,” Patel said in the press release.¹

REFERENCES

1. CHMP recommends RYBREVANT (amivantamab) in combination with LAZCLUZE (lazertinib) for the first-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer. Johnson & Johnson. News release. November 15, 2024. Accessed November 18, 2024. https://www.globenewswire.com/news-release/2024/11/15/2982110/0/en/CHMP-recommends-RYBREVANT-amivantamab-in-combination-with-LAZCLUZE-lazertinib-for-the-first-line-treatment-of-patients-with-EGFR-mutated-advanced-non-small-cell-lung-cancer.html.

2. Ferruggia K. Researchers Begin Phase 3 Trial Assessing Adjuvant V940 With Pembrolizumab to Treat Non–Small Cell Lung Cancer. Pharmacy Times. News release. October 29, 2024. Accessed November 18, 2024. https://www.pharmacytimes.com/view/researchers-begin-phase-3-trial-assessing-adjuvant-v940-with-pembrolizumab-to-treat-non-small-cell-lung-cancer.