Out of a total of 1074 randomized participants, 629 were of Asian descent, with 250 assigned to the amivantamab-lazertinib (ami-laz) arm and 251 to the osimertinib (osi) arm. Among Asian participants, the median age was 63 years, with 61% and 57% being female, and 44% and 43% having a history of brain metastases in the ami-laz and osi arms, respectively. With a median follow-up of 22.5 months, ami-laz exhibited a 35% reduction in the risk of disease progression or death compared to osi in Asian participants. The median progression-free survival (PFS) was 27.5 months for ami-laz, which was comparable to the overall study population. The overall response rate (ORR) was 88% for ami-laz compared to 85% for osi. Among confirmed responders, the median duration of response (mDoR) was 26.1 months for ami-laz and 17.5 months for osi. Notably, amivantamab + lazertinib improved median DoR by 8.6 months, suggesting a longer time for resistance and progression. In the safety assessment, amivantamab + lazertinib exhibited elevated rates of grade ≥3 adverse events (71%) and dose adjustments compared to osimertinib. Additionally, 9% of patients experienced treatment-related adverse events leading to discontinuation of amivantamab + lazertinib. Moreover, the adverse event (AE) rates in Asian participants were similar to the broader study population. While EGFR- and MET-related AEs were higher for ami-laz, except for diarrhea, which was higher for osi. Venous thromboembolism (VTE) rates were increased for ami-laz, mostly grade 1-2 events occurring in the first 4 months and effectively managed with anticoagulants. The incidence of interstitial lung disease (ILD) was low and comparable across both treatment arms.

KOL insights

"RYBREVANT is a first-in-class bispecific antibody that targets major oncogenic driver pathways and, when combined with lazertinib, may lead to a more complete and synergistic response against the tumor," –Expert Opinion.

Conclusion

Marking a significant stride, amivantamab + lazertinib emerges as a breakthrough in first-line treatment for EGFR-mutant advanced NSCLC among Asian patients, demonstrating substantial improvements in progression-free survival over osimertinib. This solidifies amivantamab + lazertinib as the new standard of care in the initial stages of EGFR-mutant advanced NSCLC.

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.