RYBREVANT (amivantamab) is a dual-action antibody designed to target EGFR and MET, alongside its ability to direct immune cells. In the MARIPOSA clinical trial, this antibody was used in combination with lazertinib, a third-generation oral EGFR tyrosine kinase inhibitor, to treat patients with non-small cell lung cancer (NSCLC) that harbored EGFR mutations and had reached advanced or metastatic stages. The study involved 1,074 patients who were randomly assigned to one of three treatment groups: amivantamab plus lazertinib, osimertinib alone, or lazertinib alone. The primary objective of the study was to assess progression-free survival (PFS) in patients treated with amivantamab and lazertinib, comparing it to the outcomes of those treated with osimertinib alone. Secondary measures included overall survival (OS), objective response rate (ORR), duration of response (DOR), and progression-free survival within the brain (intracranial PFS).

When considering cases where central nervous system (CNS) progression was the initial sign of disease advancement, the median progression-free survival (PFS) for patients receiving the combination therapy of amivantamab and lazertinib was 27.5 months, in contrast to 18.5 months for those treated with osimertinib. Additionally, the median duration of response (DOR), which denotes how long a tumor remains responsive to treatment without further growth or spread, was notably prolonged for patients treated with amivantamab and lazertinib when compared to those on osimertinib, with a substantial nine-month increase in the median DOR.

	Amivantamab + Lazertinib (n=429)	Osimertinib (n=429)
ORR
All responders	86%	85%
Confirmed responders	80%	76%
Best response
CR	7%	4%
PR	79%	81%
SD	7%	10%
PD	2%	3%
NE/UNK	5%	3%
Median DoR	25.8 months	16.8 months
ORR, objective response rate; CR, complete response; PR, partial response; PD, progressive disease; SD, stable disease; NE/UNK, not evaluable/unknown; DoR, duration of response

The safety results of the study revealed that the median treatment duration for amivantamab + lazertinib was 18.5 months, while for osimertinib, it was 18.0 months. Treatment-related adverse events (AEs) leading to discontinuation of all medications occurred in 10% of patients receiving amivantamab + lazertinib and 3% of those taking osimertinib. The safety profile of amivantamab + lazertinib was consistent with previous reports, primarily consisting of grades 1-2 AEs. EGFR and MET-related AEs were more common in patients treated with amivantamab + lazertinib, except for diarrhea, which had a higher incidence with osimertinib. The occurrence of severe (Grade 4-5) AEs was low and similar between the two treatment arms. Rates of interstitial lung disease/pneumonitis remained low, at approximately 3% for both treatment groups.

KOL insights: “The MARIPOSA trial highlights the potential of Amivantamab and Lazertinib combination as a promising first-line treatment for EGFR-mutated NSCLC, offering improved progression-free survival while maintaining a comparable safety profile to Osimertinib.” – MD, MPH, US

Conclusion: NSCLC accounts for up to 85% of lung cancer. DelveInsight estimates that approximately 3,500 patients had exon 20 insertion EGFR mutation in the United States in 2022.

The MARIPOSA clinical trial evaluated the efficacy and safety of the dual-action antibody RYBREVANT (amivantamab) in combination with lazertinib for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations in advanced or metastatic stages. This combination therapy demonstrated significant improvements in key clinical outcomes compared to osimertinib alone, with a notably prolonged median progression-free survival (PFS) of 27.5 months and a substantial nine-month increase in the median duration of response (DOR). The objective response rate (ORR) was also favorable for the combination therapy. The safety profile of amivantamab + lazertinib was consistent with prior reports, with mostly manageable grades 1-2 adverse events. These findings suggest that the combination of amivantamab and lazertinib holds promise as an effective and well-tolerated treatment option for EGFR-mutated NSCLC patients.

For more insight into the NSCLC patient's burden/epidemiology, mutation specific treatment, and changing market landscape-related advancements, refer to the Epidermal Growth Factor Receptor-Non Small Cell Lung Cancer (EGFR-NSCLC) Market Report and Non-Small Cell Lung Cancer Market Insight and Market Forecast Report

Note: The therapeutics segment is experiencing significant NSCLC clinical trial activity, which is further expected to drive Non-Small Cell Lung Caner market growth in the coming years.