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

1. Previous severe hypersensitivity reaction to any component of study drug(s).

2. 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.

3. Genetic analysis results:

1. 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.).

2. 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.).

4. 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).

5. 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.

6. 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)

7. Prior organ or stem cell transplant.

8. 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)

1. HIV

✓ CD4+ cells ≥ 350 cells/µL

✓ No history of AIDS

✓ No history of opportunistic infection in the past 12 months

2. HCV

✓ Undetectable viral load (Participants positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for hepatitis C RNA)

3. HBV ✓ Concurrent HBV treatment and undetectable viral load (Participants with a past or resolved hepatitis B infection defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of hepatitis B surface antigen are eligible)

9. Symptomatic ascites or pleural effusion, unless clinically stable for at least two weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis).

10. Known active central nervous system (CNS) primary tumor or metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to first dose of study medication(s), have no evidence of new or enlarging brain metastases and are off steroids for at least 15 days prior to first dose of study medication(s).

11. Presence or history of a malignant disease other than disease to be treated in current protocol that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, indolent malignancies that currently do not require treatment, and completely resected carcinoma in situ of any type.

12. Active infection requiring therapy. However, subject with minor infections requiring oral antibiotics, (e.g., urinary tract infection, Upper respiratory tract infection, etc.) could be eligible based on investigator's judgement.

13. Use of systemic corticosteroids \> 10 mg/day prednisone or equivalent within 30 days or other immunosuppressive drugs within 30 days prior to first drug administration.

14. Patients receiving treatment with medications that meet one of the following criteria and that cannot be discontinued specified period prior to the start of treatment with study drug and for the duration of the study.

For Vabametkib (Wash-out: 1 week)

• Strong and moderate inhibitors/inducers of P-glycoprotein

• Strong and moderate inhibitors/inducers of CYP3A4

• Proton pump inhibitors (PPI)

• Potassium-competitive acid blockers For Lazertinib

* Strong and moderate CYP3A4 inducers

* Medications possibly prolong QT interval or induce Torsades de Pointes

15. Has received or will receive a live vaccine within 30 days prior to the first administration of study medication. Seasonal flu vaccine that does not contain live vaccine are permitted.

16. Received an investigational product (except for EGFR TKI in Cohort 2) or treated with an investigational device within 30 days prior to first study drug administration.

17. Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or tyrosine kinase inhibitors (except for EGFR TKI in Cohort 2) within 2 weeks (4 weeks in case of thoracic radiotherapy to lung fields) or 5 half-lives (whichever is longer) of the start of study treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of study treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of study treatment; 7-day washout is permitted for palliative radiation (i.e. limited field, ≤ 14-day course of radiotherapy) to non-CNS lesions.

18. History or clinical evidence of any surgical or medical condition which the investigator judges as likely to interfere with the results of the study or pose an additional risk in participating e.g., rapidly progressive or uncontrolled disease involving a major organ system-vascular, ophthalmologic, cardiac (clinically important abnormalities in rhythm, conduction or morphology of resting ECG, uncontrolled hypertension, uncontrolled symptomatic heart failure), pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, autoimmune or an immunodeficiency, or clinically significant active psychiatric or abuse disorders.

19. Is a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).

20. Patients with a corrected QT interval (using Fridericia's correction formula) (QTcF) of \> 470 msec.

21. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medications known to prolong QT interval or induce Torsades de Pointes.

22. Congestive heart failure (CHF), defined as New York Heart Association (NYHA) class III-IV or hospitalization for CHF (any NYHA class), within 6 months of randomization.

23. An active or past medical history of pericarditis, pericardial effusion that is clinically unstable, or myocarditis. Pericardial effusion considered due to the disease under study is permitted if clinically stable at Screening.

24. (for Cohort 2) Baseline LVEF either \<50% or below the lower limit of normal (LLN) per institutional guidelines, as assessed by screening echocardiogram or MUGA scan.

25. (for Cohort 2) Patients who have been receiving medications with potential for QT interval prolongation will be eligible only when the wash out period was finished.

What this study is about