SHP2 Inhibitor ET0038 Monotherapy in Patients With Advanced Solid Tumors

Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study specificprocedures, sampling and analyses.
2. Aged at least 18 years at the time of ICF signature.
3. Histological or cytological confirmation of a solid tumor and have progressed despitestandard therapy(ies), or are intolerant to standard therapy (ies), or have a tumorfor which no standard therapy(ies) exists. Locally recurrent disease must not beamenable to surgical resection or radiotherapy with curative intent (patients who areconsidered suitable for surgical or ablative techniques following down-staging withstudy treatment are not eligible).
4. Estimated life expectancy of minimum of 12 weeks.
5. Patient with solid tumors must have at least 1 lesion, not previously irradiated, thatcan be accurately measured at pre-dose as ≥ 10 mm in the longest diameter (exceptlymph nodes which must have short axis ≥ 15 mm) with Computerised Tomography (CT) ormagnetic resonance imaging (MRI) and which is suitable for accurate repeatedmeasurements.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at ICF signature.
7. Males and Females of child-bearing potential must agree to use effective contraceptionfrom the time ICF signature until 12 weeks after the last dose. Females ofchildbearing potential include those who are premenopausal and those who are 2 yearspostmenopausal. Pregnancy tests for female of child-bearing potential must have anegative serum pregnancy test at Screening.

Exclusion Criteria:

1. Central nervous system metastatic disease, leptomeningeal disease, or metastatic cordcompression.
2. As judged by the investigator, any evidence of significant ophthalmologicalabnormalities including but not limited to history or current evidence of retinal veinocclusion (RVO) or current risk factors for RVO, retinal macular degeneration,uncontrolled glaucoma, cataract or marked decrease in visual acuity, symptomaticsevere dry eye, conjunctivitis, or corneal ulcer.
3. Prior bone marrow or organ transplantation
4. Prior treatment with ET0038 or a SHP2 inhibitor.
5. Prior therapy with any investigational drugs or systemic anticancer treatment within 28 days (or a period of 5 'half-lives' of this investigational drugs or systemicanticancer treatment, whichever is the most appropriate and as judged by theinvestigator) at the time of ICF signature.
6. Radiotherapy with a wide field of radiation within 28 days, or radiotherapy with alimited field of radiation for palliation within 14 days at the time of ICF signature,or planning radical radiation therapy while participating in the study.
7. Prior major surgery (excluding placement of vascular access) within 28 days at thetime of ICF signature, or planning for major surgery while participating in the study.
8. With the exception of alopecia, any unresolved toxicities from prior therapy greaterthan Common Terminology Criteria for Adverse Events (CTCAE5.0) Grade 1 at the time ofICF signature.
9. Any uncontrolled active infection requiring parenteral administration of antibiotics,antivirals, or antifungals at the time of ICF signature and/or within one week ofCycle 1 Day 1 (C1D1).
10. Patient with a history of active pulmonary tuberculosis infection within 1 year priorto screening (as judged by investigator, active pulmonary tuberculosis infection morethan 1 year and no evidence of active pulmonary tuberculosis at present will beconsidering eligible)
11. Patient with history or presence of interstitial lung disease or interstitialpneumonitis.
12. An active, or previously, autoimmune disease that may recur (e.g., systemic lupuserythematosus, rheumatoid arthritis, inflammatory bowel disease,autoimmune thyroiddisease, vasculitis, and psoriasis etc.) or high risk to such diseases.
13. Active infection including hepatitis B (Hepatitis B surface antigen [HBsAg] positive),and/or hepatitis C (HCV-RNA positive).
14. Active human immunodeficiency virus (HIV) infection (Patient with HIV positive andhave well-controlled disease is exception).
15. Patient inability or unwillingness to comply with requirement for oral drugadministration or presence of a gastro-intestinal condition, e.g., Refractory nauseaand vomiting, inability to swallow the formulated product or previous significantbowel resection.
16. Have a history or present active bleeding disease within 6 months at the time of ICFsignature.
17. History of COVID-19 infections, or COVID-19 nucleic acid test positive at the time ofICF signature and/or prior to the first dose of study treatment.
18. Pregnant or Breast-feeding women