To Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetic Profile of ABN401 in Patients With Advanced Solid Tumors Harboring c-MET Dysregulation

NCT05541822 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ABN401-003
• Study Type: interventional
• Target: 178
• Locations: 3 countries
• Sites: 24

Brief Summary

ABN401-003 is a Phase 2 clinical study to assess efficacy, safety, tolerability and pharmacokinetic profile of ABN401 (vabametkib) in specific populations of advance solid tumors with c-MET alterations as monotherapy.

Conditions

Advanced Solid Tumors

Keywords

c-MET

Outcome Measures

Primary Outcomes (4)

• Cohort 1: Objective response rate (ORR) according to response evaluation criteria in solid tumors (RECIST)1.1 by Blinded Independent Central Review (BICR)

  ORR is defined as the proportion of patients who experience a complete response (CR) or partial response (PR) as measured by RECIST 1.1

  Up to 12 months

• Cohort 2 Part 1: Incidence of DLT (Dose Limiting Toxicity)

  Up to 12 months

• Cohort 2 Part 2: Optimal dose of vabametkib and lazertinib combination for Part 3 based on the risk-benefit assessment considering both ORR (Objective Response Rate) and AE (Adverse Events)

  Up to 12 months

• Cohort 2 Part 3: ORR (Objective Response Rate)

  Up to 12 months

Secondary Outcomes (43)

• Cohorts 1 & 2: Objective response rate (ORR) measured by RECIST 1.1 by BICR

  Up to 12 months

• Cohorts 1 & 2: Duration of response (DoR) as measured by RECIST 1.1 by BICR

  Up to 12 months

• Cohorts 1 & 2: Disease advanced control rate (DCR) as measured per RECIST 1.1 by BICR

  Week 12

• Cohorts 1 & 2: Progression-free survival (PFS) according to RECIST 1.1 by BICR

  Up to 18 months

• Cohorts 1 & 2: Overall survival (OS) according to RECIST 1.1

  Up to 18 months

Study Arms (2)

Cohort 1: Vabametkib

EXPERIMENTAL

Subjects will receive vabametkib 800 mg, monotherapy, administered orally once daily in 21-day cycles

Drug: Vabametkib

Cohort 2: Lazertinib & Vabametkib

EXPERIMENTAL

Part 1 (Safety Run-in): Subjects will receive lazertinib 240 mg in combination with one of three assigned dose levels of vabametkib, administered orally once daily in 21-day cycles Part 2 (Random Dose Optimization): A maximum of two vabametkib dose levels will be evaluated in this part. Patients will be randomized in 1:1 ratio to vabametkib dose level 1 (selected from Part 1) plus the determined dose of lazertinib or dose level 2 (selected from Part 1) plus the determined dose of lazertinib Part 3 (Randomized Clinical Trial): Patients will be randomized in 1:1 ratio to optimized vabametkib dose (selected from Part 2) plus lazertinib or Standard of Care (SOC) arm. SOC arm will be decided by the time of Part 3 initiation

Drug: Vabametkib; Drug: Lazertinib

Interventions

Vabametkib DRUG

Tablets Route of Administration: Oral

Cohort 1: Vabametkib; Cohort 2: Lazertinib & Vabametkib

Lazertinib DRUG

Tablets Route of Administration: Oral

Cohort 2: Lazertinib & Vabametkib

Eligibility Criteria

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

You may qualify if:

• Male or female ≥ 18 years of age or designated age of majority according to the regulatory authorities, whichever is higher.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS), 0 or 1.
• Have a life expectancy of at least 3 months.
• Diagnosis:
• must have histologically or cytologically confirmed NSCLC, advanced, recurrent, or metastatic,
• For Cohort 1: MET exon 14 skipping suspected by local or central biomarker assessment. \[local testing is accepted for eligibility; all patients will have confirmation by central laboratory, but this result is not necessary for eligibility; local molecular pathology result will suffice\]. This testing can be from archival or fresh tissue sample and/or blood specimen; any sample, any test positive subjects are eligible.
• For Cohort 2:
• Non-squamous histology (confirmed by histology or cytology)
• EGFR mutation-positive including exon 19 deletions or exon 21 L858R as detected by an FDA-approved or other validated test in a CLIA certified laboratory (sites in the US) or an accredited local laboratory (sites outside of the US) in accordance with site standard of care. (Note: A copy of the test report documenting the EGFR mutation must be included in the participant records and it must be reviewed by the Medical monitor.)
• Radiological documentation of disease progression while on continuous treatment with the 1st line 3rd generation EGFR-TKI
• Prior objective clinical benefit defined by either partial or complete radiological response, or durable SD (SD should last \> 6 months) from the 1st line 3rd generation EGFR-TKI
• Interval between documentation of radiological progression of disease on the 1st line 3rd generation EGFR TKI and first dose of study drug should be ≤ 60 days
• MET amplification or overexpression from tumor sample collected following progression on 1st line 3rd generation EGFR-TKI • Amplification GCN ≥ 10 indicated by FISH (confirmed centrally, slides or image from local laboratory will be confirmed by the central pathologist) or NGS (confirmed either centrally or locally) • Overexpression indicated by IHC90+ (i.e. 3+ staining in ≥ 90% tumor cells by central test, if local IHC results are available, image from local laboratory will be confirmed by central pathologist. Despite the image submission, tissue unstained slides should be sent to central laboratory for confirmation of MET amplification or overexpression.)
• Treatment experience
• Cohort 1: Anti-tumor treatment naïve subject upon refusal to receive 1st line standard of care, or not tolerated to 1st line standard of care, or progressed after standard of care with no greater than 2 prior treatment regimens (neoadjuvant, adjuvant, and maintenance therapies do not qualify as separate treatment regimens).

You may not qualify if:

• Previous severe hypersensitivity reaction to any component of study drug(s).
• Prior therapy
• a. Previous treatment with c-MET inhibitors or hepatocyte growth factor (HGF)-targeting therapy.
• b. For Cohort 2, prior chemotherapy for advanced, recurrent, or metastatic setting.
• Genetic analysis results:
• Cohort 1: Existing genetic data from the patient's tumor tissue showing known molecular alterations which would make them eligible for targeted therapies (e.g., EGFR mutations, ALK rearrangements, KRAS mutation, ROS1 translocation, BRAF mutation, RET alteration, and NTRK fusion, etc.).
• Cohort 2: Patients with known molecular alterations that can't benefit from study medication (e.g., EGFR mutation known to be associated with the resistance to 3rd generation EGFR TKIs, such as C797X or insertion 20, ALK rearrangements, KRAS mutation, ROS1 translocation, BRAF mutation, RET alteration, and NTRK fusion, etc.).
• Chronic inflammatory liver condition. History or clinical evidence of any significant liver or biliary pathology including cirrhosis, infectious disease, inflammatory conditions, steatosis, or cholangitis (including ascending cholangitis, primary sclerosing cholangitis, obstruction, perforation, fistula of biliary tract, spasm of sphincter of Oddi, biliary cyst or biliary atresia).
• Past medical history of Interstitial Lung Disease (ILD)/pneumonitis, drug-induced or radiation ILD/pneumonitis that required steroid treatment or other immune suppressive agents, or evidence of current symptomatic interstitial lung disease or unexplained pulmonary symptoms indicative of ILD such dyspnea, cough, or fever.
• Impairment of Gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, uncontrolled vomiting, uncontrolled diarrhea, or malabsorption syndrome)
• Prior organ or stem cell transplant.
• Known active infection with human immunodeficiency virus (HIV), human T-cell leukemia virus, type (HTLV-1), hepatitis B virus (HBV), or hepatitis C virus (HCV), unless the patients fall into below categories (patients fall into one of the a, b, c category are eligible to participate)
• HIV
• ✓ CD4+ cells ≥ 350 cells/µL
• ✓ No history of AIDS

Sponsors & Collaborators

• Abion Inc: lead

Study Sites (24)

Cancer Care of North Florida, PA (Lake City Cancer Care, LLC) - Medical Oncology

Lake City, Florida, 32024-3456, United States

RECRUITING

Mid Florida Center

Orange City, Florida, 32763-8316, United States

RECRUITING

The Henry Ford Cancer Institute

Detroit, Michigan, 48202, United States

NOT YET RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4000, United States

RECRUITING

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

RECRUITING

Ajou University Hospital

Suwon, Gyeonggi-do, 16499, South Korea

RECRUITING

Boramae Medical Center

Dongjak, Seoul, 07061, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, Seoul, 02841, South Korea

RECRUITING

Severance Hospital

Sinchon-dong, Seoul, 03776, South Korea

RECRUITING

Chungbuk National University Hospital

Cheongju-si, 28645, South Korea

RECRUITING

Gachon University Gil Medical Center

Incheon, 21565, South Korea

RECRUITING

Gyeongsang National University Hospital

Jinju, 52728, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

RECRUITING

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

The Catholic University of Korea, Seoul St Mary's Hospitals

Seoul, 06591, South Korea

RECRUITING

The Catholic University of Korea St Vincents Hospital

Suwon, 16248, South Korea

RECRUITING

China Medical University Hospital

Taichung, 404, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, 704, Taiwan

RECRUITING

Chi Mei Hospital, Liouying

Tainan, 736, Taiwan

RECRUITING

National Taiwan University Cancer Center (NTUCC)

Taipei, 10052, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 112, Taiwan

RECRUITING

MeSH Terms

Interventions

lazertinib

Central Study Contacts

Viki Kim

CONTACT

82-2-6006-4767; viki.kim@abionbio.com

Jeesun Kim

CONTACT

82-2-6022-6428; jeesun.kim@abionbio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2022
• First Posted: September 15, 2022
• Study Start: January 17, 2023
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

TW (6); US (4); KR (14)