LAZCLUZE·RYBREVANT Combo: A Game Changer for EGFR Mutant Lung Cancer

The combination therapy of LAZCLUZE(Lazertinib) and RYBREVANT(Amivantamab) has demonstrated superior effectiveness compared to existing monotherapies in treating atypical EGFR mutation non-small cell lung cancer (NSCLC). A study led by Professor Hong Min-hee from Yonsei Cancer Center and Professor Yoon Mi-ran from the Department of Biomedical Science, Yonsei University, revealed that the combination therapy overcame resistance and demonstrated sustained tumor suppression effects, the results of which were announced on the 11th.

Need for New Treatment for EGFR Mutant Lung Cancer
EGFR mutations are found in about 30-40% of non-small cell lung cancer (NSCLC) patients. Of these, 90% correspond to the L858R or exon 19 deletion mutations, while the remaining 10% are categorized as atypical EGFR mutations (G719X, S768I, L861Q, etc.). Atypical mutations often involve two or more mutations occurring simultaneously, complicating treatment.

Currently, EGFR-targeted therapies such as the second-generation Apatinib and third-generation Osimertinib are used, but their effectiveness is limited for some atypical mutations, highlighting the need for new treatments.

Professor Hong's team explored the potential of overcoming the limitations of current therapies by combining the third-generation EGFR-targeted therapy LAZCLUZE with the EGFR-MET dual-target antibody RYBREVANT. The researchers found in experiments using mouse cell lines, patient-derived organoids (PDO), and patient-derived cells (PDC) that the combination therapy exhibited superior tumor suppression effects compared to monotherapy.

In PDO experiments, the combination therapy reduced the drug concentration required to inhibit cancer growth (IC50) by six times compared to monotherapy, amplifying the therapeutic effect. In PDC models, antibody-dependent cell cytotoxicity (ADCC) was observed even in cells resistant to monotherapy. In animal studies, the combination therapy inhibited tumor growth for approximately 90 days after treatment cessation, demonstrating its durability.

Real-World Results: Progression-Free Survival Over 16 Months
When applied to actual patients, 40% of patients showed tumor shrinkage, and the progression-free survival (PFS) was significantly longer than with monotherapy, exceeding 16 months. This improvement was attributed to LAZCLUZE increasing target receptor expression, thereby enhancing the efficacy of RYBREVANT.

Professor Hong Min-hee stated, "This study shows that the combination therapy activates the immune system's ability to destroy cancer cells, overcoming resistance to existing therapies. It also provides a foundation for using MET mutation expression levels as a predictive biomarker for treatment response."

This study builds on the data presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting, offering both academic value and clinical significance.