Beijing Avistone Biotechnology presented encouraging clinical data at the American Society of Clinical Oncology (ASCO) Annual Meeting 2025 for its dual-target combination therapy addressing a critical resistance mechanism in lung cancer treatment. The Phase Ib/II KYLIN-1 study demonstrated that Vebreltinib plus Andamertinib (PLB1004) achieved meaningful clinical activity in patients with EGFR-mutated non-small cell lung cancer (NSCLC) who developed resistance through MET amplification or overexpression.
Clinical Efficacy Results
The study enrolled 56 patients who received the recommended Phase 2 dose of Vebreltinib 150mg twice daily plus Andamertinib 80mg once daily. The combination achieved a confirmed overall response rate of 50.0% with a median progression-free survival of 9.9 months. These results address a significant clinical challenge, as MET amplification or overexpression represents the most common "off-target" mechanism driving resistance to EGFR tyrosine kinase inhibitors in NSCLC patients.
The therapy demonstrated particular promise in patients with brain metastases, a notoriously difficult-to-treat population. Among 19 patients with central nervous system involvement, the combination achieved a 42.1% overall response rate and a median progression-free survival of 9.5 months.
Safety Profile
The safety profile proved manageable across the study population. Grade 3 or higher treatment-related adverse events occurred in 19.6% of patients, with no treatment discontinuations or deaths attributed to therapy-related toxicity. The study investigators reported no new safety signals beyond the known profiles of the individual agents.
Mechanism of Action
Vebreltinib functions as an orally administered, potent and selective c-Met inhibitor, while Andamertinib (PLB1004) serves as an oral, irreversible, and selective EGFR tyrosine kinase inhibitor with enhanced blood-brain barrier penetration. Preclinical studies have demonstrated Andamertinib's ability to effectively target exon 20 insertions and classical EGFR mutations including Del19, L858R, and T790M with high selectivity.
Regulatory Status and Future Development
Vebreltinib has already received approval from the Chinese National Medical Products Administration for locally advanced or metastatic NSCLC patients with MET exon 14 skipping mutations, as well as for specific brain tumor indications involving PTPRZ1-MET fusion genes. The Chinese Center for Drug Evaluation has accepted a New Drug Application for Vebreltinib in NSCLC with MET amplification and granted it priority review status.
Phase III Development
Building on these Phase Ib/II results, Avistone has initiated the multicenter Phase III KYLIN-3 study (NCT06970782). This randomized trial will evaluate Vebreltinib plus Andamertinib versus platinum-based doublet chemotherapy in patients with EGFR mutations, MET amplification and/or overexpression, and locally advanced or metastatic NSCLC following EGFR-TKI failure.
The KYLIN-1 study results were presented as poster 8632 during the Lung Cancer-Non-Small Cell Metastatic session at ASCO 2025, highlighting the growing recognition of combination approaches to overcome resistance mechanisms in precision oncology.
