A Study to Evaluate ANS014004 in Subjects With Locally Advanced or Metastatic Solid Tumors

Inclusion Criteria:

1. Male or female subjects, ≥18 years of age at the time of signing the informedconsent form.

2. Participants with a histologically confirmed diagnosis of unresectable locallyadvanced or metastatic solid tumors, relapsed or refractory to existing standardtherapy, intolerant or unsuitable for existing standard therapy, or for whom nostandard therapy is available (standard therapy is defined as therapy recommended byestablished guidelines and consensus [including, but not limited to, chemotherapy,radiotherapy, targeted therapy based on mutation status, immunotherapy, andsurgery]). Locally advanced participants must be ineligible for radical surgery orradiotherapy. Participants who are intolerant of or unsuitable for existing standardtherapy or for whom no standard therapy is available will be required to documentthese reasons.

3. Documentary evidence of pathogenic MET alterations from a local laboratoryaccredited by the Clinical Laboratory Improvement Act Amendments (CLIA), theInternational Organization for Standardization/Independent Ethics Committee (ISO/IEC), the College of American Pathologists (CAP), or other equivalentaccreditation. Part 1 Specific Inclusion Criteria: Subjects carrying pathogenic METalterations (including MET mutations, MET amplification, MET overexpression, METfusions) will be enrolled. Part 2 Specific Inclusion Criteria: Subjects will beenrolled into one of the following 5 cohorts based on tumor type, MET alterationstatus, and prior therapy. Cohort 1: Subjects must have pathologically confirmed,diagnosed NSCLC with a MET exon 14 jump mutation, with or without other METalterations, and prior treatment with an approved MET-TKI (e.g., camatinib andtopotecanib). Cohort 2: Subjects must have pathologically confirmed, diagnosed NSCLCwith a MET exon 14 jump mutation, with or without other MET alterations, relapsed orrefractory to platinum-based chemotherapy, or intolerant or unsuitable forplatinum-based chemotherapy, and have not received a prior MET-TKI. Cohort 3:Subjects must have pathologically confirmed, diagnosed NSCLC with a METamplification, no MET exon 14 jump mutation, relapsed or refractory toplatinum-based agent chemotherapy, intolerant to platinum-based agent chemotherapy,or unsuitable for platinum-based agent chemotherapy. Cohort 4: Subjects must havepathologically confirmed, diagnosed solid tumors (other than NSCLC) with MET exon 14jump mutations, with or without other MET alterations, relapsed or refractory tostandard therapy, or intolerant or unsuitable for standard therapy, or no standardtherapy available. Cohort 5: Subjects must have a pathologically confirmed,diagnosed solid tumor with MET amplification (except NSCLC) or overexpression orfusion, without MET exon 14 jump mutations, relapsed or refractory to standardtherapy, or intolerant or unsuitable for standard therapy, or no standard therapyavailable.

4. At least one measurable target lesion as defined by RECIST v1.1 (Appendix 3). (except for the low dose groups 7.5mg and 15mg).

5. Part 1 ECOG PS ≤ 1; Part 2 ECOG PS ≤ 2.

6. expected survival of ≥ 12 weeks in the judgment of the investigator.

7. Good organ function as determined by medical evaluation (within 7 days prior tostudy treatment), including: Good hematologic status, defined as: absoluteneutrophil count (ANC) ≥ 1.5 x 10 9/L, hemoglobin ≥ 90 g/L, and platelets ≥ 75 x 109/L. Receipt of platelet transfusions is not permitted within 3 days prior totesting, erythrocyte transfusions within 14 days prior to testing, and hematopoieticgrowth factors (polyethylene glycolized granulocyte colony-stimulating factor [G-CSF] or erythropoietin is within 14 days prior to testing) within 7 days prior totesting. Hematopoietic growth factors (polyethylene glycolated granulocytecolony-stimulating factor [G-CSF] or erythropoietin for up to 14 days prior totesting) are not allowed within days. Good hepatic function, defined as serum TBIL ≤ 1.5 x ULN (TBIL ≤ 3 x ULN with direct bilirubin ≤ 1.5 x ULN in subjects known tohave Gilbert's syndrome), and serum ALT or AST ≤ 2.5 x ULN (or 5.0 x ULN insubjects with confirmed liver metastases). Good renal function, defined ascreatinine clearance ≥ 50 mL/min (measured or calculated by the Cockcroft-Gaultformula [Appendix 4]). Good coagulation function, defined as (including whenreceiving anticoagulation): prothrombin time (PT) < 1.5 x ULN and activatedpartial thromboplastin time (APTT) < 1.5 x ULN If subjects are receivinganticoagulation, they must have received a stable dose of anticoagulant for at least 1 month prior to study treatment.

8. Female subjects should use adequate contraception until 90 days after EOT, shouldnot be breastfeeding, and must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test within 7 days prior to initiation of dosing for femalesubjects of childbearing potential; female subjects of childless potential must meetone of the following criteria at screening: Postmenopausal defined as amenorrhea forat least 12 months after cessation of all exogenous hormone therapy (if applicable).applicable) followed by amenorrhea for at least 12 months. Irreversible surgicalsterilization such as hysterectomy, bilateral salpingo-oophorectomy, or bilateralsalpingo-oophorectomy (as opposed to tubal ligation) has been clearly documented.

9. Male subjects whose female partners are of childbearing potential are required touse adequate contraception (i.e., barrier methods) during study participation andfor 90 days after EOT. Male subjects must also refrain from sperm donation duringstudy participation and for 90 days after the last dose of study treatment.

10. Be able to provide signed informed consent and comply with the requirements andlimitations outlined in the Informed Consent Form (ICF) and in this study.

Exclusion Criteria:

1. for dose extension only (Part 2): known major driver gene alterations other thanMET. For example, NSCLC harboring targeted alterations such as EGFR, ALK, RET, ROS1,BRAF, KRAS, etc. Investigators should discuss enrollment with sponsors regardingco-mutations.

2. Prior treatment with other type II MET-TKIs such as cabozantinib, glitinib, andmelatinib (type II MET-TKIs are multi-targeted inhibitors that bind to the inactiveconformation (DFG-out) of MET in the ATP pocket).

3. Participation in another therapeutic clinical trial within 28 days prior to thefirst study dose.

4. Received antineoplastic therapy (chemotherapy, immunotherapy, hormone therapy,targeted therapy, biologic therapy, or other antineoplastic therapy, except forhypothyroid hormone or estrogen replacement therapy, anti-estrogen analogs, oragonists required for suppression of serum testosterone levels) within 14 days or 5half-lives (whichever is shorter) of the first dose of study treatment. Thefollowing exceptions apply: 1) Received nitrosourea or mitomycin C within 6 weeksprior to the first dose of study treatment. 2) Received a proprietary medicine withan antitumor indication within 7 days prior to the first dose of study treatment.

5. has received wide-field radiotherapy within 28 days prior to the first dose of studytreatment or has received palliative localized radiotherapy within 14 days prior tothe first dose of study treatment. Subjects must have recovered from allradiotherapy-related toxicities and not require corticosteroids.

6. Underwent major surgery (excluding diagnostic procedures) within 4 weeks prior tothe initial study treatment, or is expected to require major surgery during thestudy period.

7. Toxicity from prior therapy has not subsided to ≤ Grade 1 or baseline levels asevaluated by NCI-CTCAE v5.0. Note: For certain Grade 2 toxicities (e.g., alopecia,skin pigmentation, neuropathy), subjects may be enrolled if the toxicity is stableand does not compromise the safety of participation in this study.

8. History of another primary solid tumor diagnosed or requiring treatment within thepast 3 years (with the exception of localized basal cell or squamous cell carcinomaof the skin that has been adequately treated; or any other carcinoma in situcurrently in complete remission).

9. Presence of CNS metastases that are known to be symptomatic or clinically unstableor that require an increased steroid dose to manage central nervous system (CNS)symptoms within 4 weeks prior to the first study dose. Note: Subjects withsymptomatic CNS metastases may be enrolled in the study after treatment and controlof their symptoms provided they have been clinically stable for at least 2 weeks,have no evidence of new brain metastases or enlargement of brain metastases, andhave not had an increase in steroid dose to manage CNS symptoms within 4 weeks priorto the first study dose. Persons with comorbid carcinomatous meningitis or meningealspread or spinal cord compression were not eligible for enrollment, regardless ofwhether they were clinically stable.

10. The subject is receiving an unstable or escalating dose of corticosteroids. Forsubjects receiving corticosteroids for endocrine defects or disease-related symptoms (excluding CNS disease), the dose must have been stabilized (or lowered) for atleast 14 days prior to the first dose of study treatment.

11. the presence of any evidence of severe or uncontrolled systemic disease, as judgedby the investigator, including, but not limited to: uncontrolled hypertension,defined as a systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥100 mmHgdespite medication. for subjects with a history of hypertension, enrollment ispermitted if the BP is stable and is controlled within these limits withantihypertensive therapy. Prior history of, or current clinical symptoms of,interstitial lung disease or interstitial pneumonia, or high risk of interstitiallung disease or interstitial pneumonia, including radiation pneumonitis (i.e.,interfering with activities of daily living or requiring therapeutic intervention).Unstable or decompensated respiratory and renal disease, active bleeding disorders.

12. Serious cardiovascular or cerebrovascular disease including, but not limited to:Mean Fridericia formula-corrected QT intervals (QTcF) > 470 ms obtained on threerepetitions of 12-lead electrocardiograms (ECGs) at rest Symptomatic heart failurewith a New York Heart Association (NYHA) cardiac function classification of class IIor higher. Echocardiographic (ECHO) assessment showing a baseline left ventricularejection fraction (LVEF) below the lower limit of institutional normal (LLN) or < 50%. Any clinically significant rhythmic, conduction, or morphologic abnormality asdemonstrated by resting ECG results, e.g., complete left bundle branch block,third-degree heart block, ventricular arrhythmia requiring antiarrhythmic therapy.Any of the following within 6 months prior to the first dose of study treatment:myocardial infarction, severe/unstable angina, coronary artery bypass grafting,congestive heart failure, cardiomyopathy, pulmonary embolism, cerebral vascularaccident, or transient ischemic attack.

13. Presence of uncontrolled co-infections including, but not limited to: activehepatitis B virus (HBV) or hepatitis C virus (HCV) infection. If hepatitis B surfaceantigen (HBsAg) positive, HBV DNA testing should be performed. Subjects may beeligible to participate in the study if HBV DNA is <500 IU/ml or if the testvalue is below the lower limit of detection at the study center. (Subjects withprimary liver cancer may be eligible for enrollment if HBV DNA <2000IU/ml) If HCVantibody is positive, HCV ribonucleic acid (RNA) testing should be performed. If HCVRNA is negative, the subject may be eligible for the study. Known humanimmunodeficiency virus (HIV) infection or known history of acquired immunodeficiencysyndrome (AIDS), HIV positive. Active tuberculosis infection. Active infectionrequiring systemic therapy that occurred within 14 days prior to the first dose ofstudy treatment.

14. Unwillingness or inability to comply with oral drug administration requirements orthe presence of gastrointestinal disorders such as refractory nausea and vomiting,any acute or chronic gastrointestinal disorder, inability to swallow preparations,or previous major colectomy may prevent adequate absorption of ANS014004.

15. Concomitant use of drugs metabolized by P-glycoprotein (P-gp)/Breast cancerresistance protein (BCRP) or OCT2/OATP1B1/MATE1 within five half-lives prior to theadministration of study therapy, or treatment with potent inducers or inhibitors ofCYP2B6, CYP2C9, CYP2C19, OCT2, OATP1B1, or MATE1. For dose escalation only:Treatment with moderate or strong inducers or inhibitors of CYP2C8, CYP2D6, orCYP3A4 during the five half-lives preceding the administration of study therapy.

16. Combined use of acid-regulating drugs (e.g., proton pump inhibitors [PPIs] and H2blockers) within 5 half-lives prior to use of study treatment.

17. Presence of pleural effusion, pericardial effusion or ascites requiring drainageand/or causing severe clinical symptoms (e.g., causing shortness of breath,tachycardia, etc.).

18. Previous or ongoing severe retinopathy.

19. History of allergic reaction to ANS014004 or its excipients, or to drugs with asimilar chemical or biological structure or class to ANS014004.

20. received any live attenuated vaccination within 30 days prior to the first dose ofstudy treatment.

21. known to have a psychiatric or substance abuse disorder that may affect thesubject's compliance with the study.

22. The subject has a pre-existing or persistent clinically significant disease, medicalcondition, surgical history, abnormal physical examination findings, or laboratorytests that, in the opinion of the investigator, are not in the best interest of thesubject; or may alter the absorption, distribution, metabolism, or excretion of thestudy treatment; or impair the assessment of the study results.

23. unwillingness or inability to comply with the study procedures and study limitationsor which, in the investigator's judgment, would make the subject unsuitable forparticipation in this study.