Inclusion Criteria:
* Males and females at least 18 years of age at the time of consent (ie, screening), or according to local regulatory requirement if the legal age for consenting for study participation is more than 18 years.
* Life expectancy ≥12 weeks as judged by the Investigator.
* Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; except for Phase1a that can enroll patients with either measurable and/or non-measurable disease.
* Eastern Cooperative Oncology Group (ECOG) 0 or 1.
* Able to swallow capsules.
* Histologically or cytologically documented advanced solid tumor for which no effective standard therapy exists, or standard therapy has failed (Phase 1a).
* Histologically or cytologically documented advanced solid tumor for which no effective standard therapy exists, and for which standard therapy containing an anti-PD-(L)1 agent has failed after an initial response or stabilization of at least 4-month duration (Phase 1b and 2a).
* Adequate hematological function, coagulation defined by:
1. Absolute neutrophil count ≥1,500 cells/μL
2. Platelet count ≥100,000/μL
3. Hemoglobin ≥9.0 g/dL
4. International normalized ratio \<1.5 × the upper limit of normal (ULN)
* Adequate hepatic and renal functions defined by:
1. Total bilirubin ≤1.5 × ULN
2. AST and ALT ≤3 × ULN; if liver metastases are present, then ≤5 × ULN is allowed
3. Estimated creatinine clearance \>60 mL/min according to the Cockcroft-Gault formula
* Able to understand and to comply with all protocol requirements, instructions, and restrictions.
* QT interval corrected using Fridericia's formula (QTcF) interval ≤460 msec on screening ECG.
* Normal ejection fraction (within the reference range of the institution).
* A washout period of 4 weeks for any biologic material and a minimum of 5 half-lives for any chemotherapy is required prior to the start of treatment with resolution of any toxicity to maximum Grade 1 (except alopecia)
* Completion of radiotherapy at least 14 days prior to the start of treatment with resolution of any toxicity to maximum Grade 1
* Female patients of childbearing potential must have a negative serum pregnancy test within 7 days of the first administration of study treatment. For the purpose of this study, female patients of childbearing potential are defined as all female after puberty unless they are postmenopausal for at least 1 year, or are surgically sterile (hysterectomy or bilateral oophorectomy or tubal ligation)
Exclusion Criteria:
* Myocardial infarction within 6 months prior to screening, or pericardial effusion.
* History of cardiac or aortic surgery within 6 months prior to screening.
* Unstable angina pectoris, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism; deep venous thrombosis; arterial occlusive disease in the past 12 months.
* Congestive heart failure of New York Heart Association class III/IV.
* Major arrhythmia or abnormalities identified by ECG per Investigator's judgment.
* Uncontrolled hypertension (as defined by systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg) during the screening period.
* Elevated troponin 1 levels (Grade 3) at screening or known to have persistently elevated brain natriuretic peptide.
* Active and clinically significant bacterial, fungal, or viral infection, including active or known history of hepatitis B virus (defined as hepatitis B surface antigen \[HbsAg\] reactive), or known active hepatitis C virus (defined as hepatitis C virus ribonucleic acid \[qualitative\] is detected), known human immunodeficiency virus or acquired immunodeficiency syndrome related illness. However, an inactive hepatitis B virus carrier can be enrolled
* Current or history of interstitial pneumonitis.
* Uncontrolled metastatic disease to the brain or central nervous system, massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and over 50% liver involvement that is at the discretion of the Investigator. Note: Pleural effusion should be defined by Investigator's discretion.
* Known history of difficulty swallowing, malabsorption or other conditions that may reduce absorption of the product.
* Received prior treatment targeting the signaling pathway of TGF-β.
* Tumor that compresses or invades major blood vessels or tumor cavitation that in the opinion of the Investigator is likely to bleed.
* History of severe bleeding. Unable to stop anticoagulation therapy with heparin, low molecular weight heparin, vitamin K antagonists, antiplatelet agents, or factor Xa inhibitors throughout the study and for at least 28 days after the last administration of study treatment.
* Regular use of aspirin (\>325mg/day) or other non-steroidal anti-inflammatory drugs with antiplatelet activity or treatment with dipyramidole, ticlopidine, clopidogrel, or cilostazol within 10 days of first administration of study treatment.
* Moderate or severe heart valve function defect including moderate or severe valve stenosis or regurgitation.
* Evidence or history of septal aneurysm, other heart aneurysm, or any aneurysm of the major vessels.
* Active infection requiring systemic antibiotic therapy.
* Receipt of any live vaccine or live-attenuated vaccine within 30 days prior to the first drug administration and while participating the study.
* Unable to unwilling to stop use of strong inhibitors of CYP1A2, CYP2C8, and CYP3A4, and strong inhibitors of P-gp and BCRP at least 8 days prior to study entry (Day 1) or within all dose escalation cohorts.
* Unable or unwilling to stop use of gastric pH elevating agents including proton pump inhibitors, H2-recpetor antagonists and antacide at least 8 days prior to study entry (Day 1) or within all dose escalation cohorts.
* Unwilling to stop use of herbal supplements or traditional herbal medicines.
* Known substance abuse concurrent treatment with non-permitted drugs.
* Known history, or suspected hypersensitivity to any excipients of the clinical study drugs.
* Undergone major surgeries within 28 days of first dosing, or have a planned surgery during the study period.
* Female patients who are breastfeeding.
* Female patients must not be pregnant or at risk to become pregnant during the study. Fertile male and female patients must agree to use an effective barrier method of birth control to avoid pregnancy (for female patients a double-barrier method of contraception, for male patients a condom with spermicide) or total abstinence from the time of providing informed consent until 30 days after the last administration of TU2218.
* Any other serious medical condition which in the Investigator's opinion would preclude safe participation in the study.
For Anti PD1 antibody combination therapy part:
* Unable to stop chronic systemic steroid therapy or any other immunosuppressive mediacation
* Use of oral, inhaled, or topical corticosteroid, at doses \> 10mg/day prednisolone or equivalent and the dose must be stable over 4 weeks prior to Day1 of Cycle1.
* Active autoimmune disease or history of autoimmune disease, except vitiligo, hypothyroidism, or resolved childhood asthma/atropy
* Known tolerance to an anti-PD(L)1 agent during prior exposure
