2023 North America Conference on Lung Cancer (NACLC) - Posters and Abstracts-PP01.104 Peony Yu Abstract

PP01.104 Peony Yu Abstract

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A study analyzed the co-occurrence of MET exon 14 skipping mutations (METex14) and MET amplification (METamp) in non-small cell lung cancer (NSCLC) and assessed the efficacy of vebreltinib, a MET tyrosine kinase inhibitor, in METex14-mutant NSCLC with or without METamp. The study found that the majority of METex14 NSCLCs do not have co-occurring METamp. The analysis of data from the AACR Project GENIE and cBioPortal websites showed that 83.4% and 91.9% of METex14 NSCLC patients had GCN4 (no co-occurring METamp), while GCN6 (co-occurring METamp) was observed in 7.9% and 7.1% respectively. In the phase 2 studies KUNPENG and SPARTA-II, which included treatment-naïve and pretreated patients, 91.6% had GCN4 and 2.4% had GCN6. The objective response rate (ORR) in patients without co-occurring METamp was 64.5% with a median duration of response (mDOR) of 15.9 months, while the ORR in patients with MET GCN4 was 85.7% with a disease control rate (DCR) of 100%. Two patients with GCN6 achieved partial response (PR). The most common treatment-related adverse events of grade 3 or higher were edema and ALT/AST increase. The study concluded that vebreltinib appears to be effective in METex14 NSCLCs with or without co-occurring METamp, including those with GCN4. The distribution of MET GCN status in vebreltinib phase 2 studies was similar to that in public databases. These findings suggest that vebreltinib could be a promising treatment option for METex14-mutant NSCLC patients.

Keywords

MET exon 14 skipping mutations

MET amplification

non-small cell lung cancer

vebreltinib

METex14-mutant NSCLC

co-occurring METamp

GCN4

GCN6

phase 2 studies

treatment-related adverse events