A Phase II Study of ABN401 in Advanced Solid Tumors With c-MET Gene Aberration
Status:
Not yet recruiting
Trial end date:
2024-12-31
Target enrollment:
Participant gender:
Summary
c-MET is a member of the receptor tyrosine kinase (RTK) family. Essential components of
signal transduction pathways regulating processes including cell proliferation,
differentiation, migration, metabolism, and cell cycle control, RTKs are established targets
as treatment strategies for various cancers. c-MET is expressed mainly in epithelial tissues
and is subject to dysregulation manifesting as mutations, amplifications, and overexpression.
c-MET is implicated in both primary oncogenesis, metastasis and also as a mechanism of drug
resistance. c-MET has a high affinity for its naturally occurring ligand, Hepatocyte Growth
Factor (HGF, also known as Scatter Factor). Binding of HGF to c-MET induces several complex
signaling pathways, resulting in cell proliferation, survival, motility, induction of cells
polarity, scattering, angiogenesis, and invasion. c-MET alterations are identified in various
cancers.
Several drugs targeting c-MET inhibition have been developed, and capmatinib was approved by
FDA in patients with non-small cell lung cancer harboring MET exon 14 skipping mutation.
ABN401 competitively attaches to the ATP binding sites in the kinase domain of c-MET with
high specificity to inhibit phosphorylation of downstream signaling pathways. Following
several animal studies of advanced solid cancers, the first-in-human trial of ABN401 showed
anti-tumor activity without DLT, and the phase 2 trial is ongoing.
Recently, the basket trials have been emphasized for tissue agnostic approach targeting
certain genetic alterations, and the NCI-MATCH (National Cancer Institute-MATCH) trials in
3,000 patients with advanced solid cancers are ongoing.
Similarly, the KOSMOS-II study is ongoing in Korea. This study is the basket trial that
Next-generation sequencing (NGS)-based genetic alterations, which is confirmed in Molecular
Tumor Board (MTB), provide the individual treatment approach.