1382P - Vebreltinib efficacy and safety in NSCLC patients with METex14 skipping mutations

Background

Approximately 3-4% of NSCLCs harbor MET exon 14 skipping mutations (METex14). Vebreltinib is a highly selective MET inhibitor (Tyrosine kinase inhibitor) in clinical evaluation for treatment of MET dysregulated tumors.

Methods

Data from two ongoing phase 2 studies, KUNPENG (NCT04258033 in China) and SPARTA-II (NCT03175224 in Global) were analyzed to explore the efficacy and safety of vebreltinib in METex14 NSCLC patients. This analysis includes 107 patients without prior exposure to MET inhibitors (71 treatment-naive and 36 previously treated NSCLC patients) who were enrolled up to April 2023. METex14 skipping mutations were confirmed centrally in all participants using next generation sequencing. All patients received vebreltinib, 200 mg BID in 28 day cycle, with 12 months of follow up data.

Results

With centrally confirmed METex14 skipping, overall response rate (ORR) to vebreltinib in treatment-naïve patients was 66.2% (95% CI: 54.0, 77.0) with median duration of response (DOR) of 16.5 months and median progression free survival (PFS) of 13.8 months. In the previously treated patients, excluding last immunotherapy use<90 days, ORR was 61.1% (95% CI: 43.5, 76.9) with median DOR of 16.7 months) and median PFS of 7.4 months. Among the 91 vebreltinib-treated NSCLC patients with METex14 for whom gene copy numbers (GCN) data was available, GCN distribution was similar to those reported in large public databases, and the ORRs by GCN continue to support vebreltinib’s efficacy, including in the GCN<4 cohort (ORR 67%; n=86) - a subgroup that is reportedly less responsive to other MET inhibitors. Similarly, ORR was 69% in GCN<6 (n=90) and 100% (1/1) in GCN>6 cohorts. Treatment-related adverse events (TRAE) of grade 3 or higher were reported in 47.7% of patients, with the most common being edema (15.9%). No death was reported due to TRAEs.

Conclusions

Vebreltinib is efficacious in NSCLC patients with centrally confirmed METex14 skipping, with an acceptable safety profile. Additionally, vebreltinib appears equally efficacious in patients with and without over-lapping MET amplifications.

Clinical trial identification

KUNPENG Study (NCT04258033 in China) and SPARTA-II Study (NCT03175224 in Global).

Editorial acknowledgement

Legal entity responsible for the study

Apollomics, Inc. and Beijing Avistone Biotechnology, Inc.

Funding

Apollomics, Inc. and Beijing Avistone Biotechnology, Inc.

Disclosure

K.P. Yu: Financial Interests, Personal, Sponsor/Funding: Apollomics. All other authors have declared no conflicts of interest.