c-MET Inhibitor in Advanced Solid Tumors With c-MET Gene Aberration

NCT05882292 | Recruiting Phase 2 DMC

• 1 other identifier: 4-2023-0093
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Neoplasms

Keywords

ABN401; c-MET gene aberration; solid tumors

Outcome Measures

Primary Outcomes (1)

• Disease control rate (DCR) at 16 weeks

  Disease control rate (DCR) at 16 weeks

  Disease control rate (DCR) at 16 weeks

Secondary Outcomes (4)

• Overall survival (OS)

  1 year

• Progression-free survival (PFS)

  at 16 weeks

• Objective response rate (ORR)

  at 16 weeks

• Duration of response (DoR)

  at 16 weeks

Study Arms (1)

ABN401

EXPERIMENTAL

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.

Drug: ABN401

Interventions

ABN401 DRUG

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.

Also known as: c-MET inhibitor

ABN401

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent for KOSMOS-II master observation study
• Male or female ≥19 years of age
• Histologically confirmed advanced solid cancers who harboring c-MET alterations (patients who performed NGS tests and c-MET alterations confirmed in molecular tumor board \[MTB\]) - exon 14 skipping mutation except for non-small cell lung cancer (NSCLC)
• c-MET amplification GCN (gene copy no.) ≥6 by NGS
• Fluorescence/Silver In situ hybridization (FISH/SISH) result of the MET/CEP7 ratio ≥2
• Other MET alterations that are regarded to be actionable by the KOSMOS MTB
• Disease progression during or after standard therapy and without further treatment options, or no standard therapy, or ineligible for standard therapy
• At least one measurable or evaluable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Eastern Cooperative Oncology Group Performance Status 0-2
• Capable to eat food
• Adequate organ functions
• Absolute neutrophil count (ANC) ≥1500/mm3 (ie, 1.5×109/L by International - Unit \[IU\]); excluding measurements obtained within 7 days after administration of granulocyte colony stimulating factor (G-CSF)
• Platelet count ≥75000/mm3 (IU: ≥75×109/L); excluding measurements obtained within 7 days after transfusion of platelets.
• Hemoglobin value of ≥8.0 g/dL
• AST/ALT ≤3×upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST / ALT ≤5×ULN

You may not qualify if:

• Previous treatment with c-MET inhibitor
• NSCLC with c-MET exon 14 skipping mutation
• Previous hypersensitivity reaction to any component of study drugs
• Presence or history of arrhythmia
• Past history of
• ① Major surgery within 4 weeks before study (must have complete recovery from surgical complications)
• ② Radiotherapy within 4 weeks before study or limited radiotherapy within 2 weeks
• ③ Chemotherapy or biologic agents within 3 weeks before study (targeted therapy within 2 weeks and mitomycin within 5 weeks)
• History of the following medical conditions
• Active central nervous system (CNS) metastasis (clinically unstable after stopping steroid for more than 2 months)
• Leptomeningeal metastasis
• Acute systemic infection
• Acute myocardial infarction, stable/unstable angina, symptomatic heart failure ((New York Heart Association \[NYHA\] class III or IV within the previous 6 months; if \>6 months cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms)
• Clinically critical chronic vomiting or diarrhea
• Uncontrolled hypertension (systolic blood pressure \>150mmHg diastolic blood pressure\>100mmHg)

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

minkyu Jung

Seoul, Seoul, 03722, South Korea

RECRUITING

MeSH Terms

Conditions

Neoplasms

Study Officials

• minkyu Jung

  Yonsei Cencer center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

minkyu Jung

CONTACT

0222278406; minkjung@yuhs.ac

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: ABN401

Study Record Dates

• First Submitted: May 11, 2023
• First Posted: May 31, 2023
• Study Start: November 10, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: December 20, 2024

Record last verified: 2024-12

Locations

KR (1)