Ignite Creation Date:
2025-12-24 @ 3:28 PM
Ignite Modification Date:
2025-12-28 @ 1:27 AM
Study NCT ID:
NCT05882292
Status:
RECRUITING
Last Update Posted:
2024-12-20
First Post:
2023-05-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
c-MET Inhibitor in Advanced Solid Tumors With c-MET Gene Aberration
Sponsor:
Yonsei University
Organization:
Study Overview
Official Title:
A Phase II Study of ABN401 in Advanced Solid Tumors With c-MET Gene Aberration
Status:
RECRUITING
Status Verified Date:
2024-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Detailed Description:
Α. Dose and cycle
\- ABN401 800 mg will be administered orally once daily immediately after a meal \[should be within 1 hour post-meal (fed state)\] at approximately the same time each day in a 21-day cycle.
Β. Treatment duration
* ABN401 will be administered until disease progression, unacceptable toxicity, death, and consent withdrawal.
* Step I: enrolled 8 patients will receive ABN401
* Step II: if more than 3 out of 8 patients showed disease control (complete response, partial response, and stable disease), step II will be forwarded and additional 10 patients will be enrolled.
* If more than 7 out of 18 patients showed disease control, ABN401 will be considered an effective drug in this study.
\- ABN401 800 mg will be administered orally once daily immediately after a meal \[should be within 1 hour post-meal (fed state)\] at approximately the same time each day in a 21-day cycle.
Β. Treatment duration
* ABN401 will be administered until disease progression, unacceptable toxicity, death, and consent withdrawal.
* Step I: enrolled 8 patients will receive ABN401
* Step II: if more than 3 out of 8 patients showed disease control (complete response, partial response, and stable disease), step II will be forwarded and additional 10 patients will be enrolled.
* If more than 7 out of 18 patients showed disease control, ABN401 will be considered an effective drug in this study.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: