A Study of ES014 (Anti-CD39/TGF-β Bispecific Antibody) in Patients With Locally Advanced or Metastatic Solid Tumors

Key Inclusion Criteria 1. To be eligible for study entry, subjects must satisfy all of the following criteria: 2. Capable of giving signed informed consent. 3. Part 1: Histological or cytological documentation of unresectable locally advanced or metastatic solid tumors, if 1) disease has progressed despite standard therapy, and no further standard therapy exists; or 2) standard therapy has proven to be ineffective or intolerable. Part 2: Histological or cytological documentation of PDAC (Cohort 2A), CRC (Cohort 2B), or NSCLC (Cohort 2C), with unresectable locally advanced or metastatic disease, if 1) disease has progressed despite standard therapy, and no further standard therapy exists; or 2) standard therapy has proven to be ineffective or intolerable. 4. Provide tumor tissue samples (minimum 10 unstained FFPE slides) obtained from the initial diagnosis to study entry. 5. At least one measurable lesion per RECIST v1.1. 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. * Part 1: ECOG PS 0-1. * Part 2: ECOG PS 0-2. 7. Life expectancy of at least 12 weeks. 8. Adequate hematologic, hepatic, renal and coagulation functions per protocol 9. Male and female subjects of childbearing potential must be willing to completely abstain or agree to use a highly effective method of contraception Key Exclusion Criteria 1. Any prior therapy targeting CD39, CD73, adenosine A2A receptor, or TGF-β. 2. Receipt of any investigational agents or devices within 4 weeks prior to the first dose of study drug. 3. Prior treatment with the following therapies: 1. Anticancer therapy within 30 days or 5 half-lives of the drug prior to the first dose of study drug, whichever is shorter. At least 14 days must have elapsed between the last dose of prior anticancer agent and the first dose of study drug is administered. Exception: hormonal and/or hormonal replacement therapy. 2. A wash out of at least 2 weeks before the start of study drug for radiation to the extremities and 4 weeks for radiation to the chest, brain, or visceral organs is required. 4. Prior allogeneic or autologous bone marrow transplantation or solid organ transplantation. 5. Toxicity from previous anticancer treatment per protocol. 6. Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug. 7. Subjects who received transfusion of blood products (including platelets or red blood cells), G-CSF, GM-CSF, recombinant erythropoietin, or recombinant thrombopoietin within 14 days prior to the first dose of study treatment. 8. Major surgery within 4 weeks prior to the first dose of study treatment. 9. Live vaccine therapies within 4 weeks prior to the first dose of study treatment. 10. Recent history of allergen desensitization therapy within 4 weeks prior to the first dose of study treatment. 11. Known allergies to CHO-produced antibodies, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to ES014. 12. Invasive malignancy or history of invasive malignancy other than disease under study within the last two years per protocol. 13. CNS metastases. 14. Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications per protocol. 15. Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications. 16. Active infection requiring systemic therapy, known human immunodeficiency virus (HIV) infection, or positive test for hepatitis B active infection (HBsAg) or hepatitis C active infection (hepatitis C antibody). 17. Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment). 18. History or evidence of cardiac abnormalities per protocol.