Inclusion Criteria:
1. Males or females, age 18 years or older.
2. Histologically confirmed diagnosis of locally advanced or metastatic solid tumor. For Part 2, subjects must have one of the following locally advanced or metastatic tumor types: hepatocellular carcinoma (HCC), colorectal cancer (CRC) with liver metastasis, urothelial cancer, squamous cell carcinoma of the head and neck (SCCHN), adenocarcinoma of the pancreas, non-small cell lung cancer (NSCLC), dMMR/MSI-High tumor (Part 2c only).
3. Subject must have exhausted all available therapy or have declined treatment or treatment is contraindicated. Subjects with tumors that have known actionable molecular alteration such as EGFR, ALK, ROS-1, BRAF, RET, MET, and KRAS must have progressed on directed molecular therapy. For Part 2c, participants with a tumor type for which a CPI has been approved must have received a CPI during one or more lines of therapy.
4. Measurable disease (at least 1 measurable lesion) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as defined by tumor type.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy of at least 3 months.
7. Female subjects must be of non-childbearing potential (surgically sterile or at least 2 years postmenopausal) or agree to use a highly effective contraception method while receiving treatment with Decoy20 and for 30 days after the last dose of Decoy20.
8. Male subjects must utilize reliable contraceptive precautions for the duration of Decoy20 treatment and 30 days after the last dose of Decoy20.
9. Adequate organ function as demonstrated by baseline laboratory assessment.
10. Left ventricular ejection fraction (LVEF) ≥ 45% by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA).
11. Recovered from toxicities due to prior therapies.
12. Willing and able to comply with all scheduled visits, laboratory tests, and other study procedures including mandatory pre-treatment and on- treatment biopsies for subjects enrolled to Part2.
Exclusion Criteria:
1. Pregnant or lactating females.
2. Has an active systemic (viral, bacterial, or fungal) infection or requiring treatment.
3. Received radiotherapy within 28 days of the first dose of Decoy20. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
4. Received prior chemotherapy, targeted therapy or immunotherapy within 28 days or 5 half-lives from W1D1, whichever is shorter.
5. Received systemic corticosteroid therapy \> 5 mg/day of prednisone or equivalent dose of another corticosteroid within 1 week or 5 half-lives (whichever is shorter) from the start of study drug or is expected to require it during the course of the study (topical and inhaled steroids are permitted).
6. Has radiographically detected primary central nervous system (CNS) metastases or symptomatic CNS involvement (including leptomeningeal carcinomatosis, cranial neuropathies or mass lesions that cause spinal cord compression). Participants with brain metastases (either treated or deemed unnecessary to treat) that have been stable by neuroimaging for at least 4 weeks will be eligible.
7. Clinical evidence of significant coagulopathy during Screening (e.g., deep vein thrombosis or pulmonary embolism) or history of significant uncontrolled coagulopathy (participants with HCC must have prothrombin time (PT) \< 4 seconds above ULN or international normalized ratio \[INR\] \< 1.7) or participants with diagnosis of a new thrombotic event within 90 days prior to Decoy20 dosing.
8. Has an active secondary malignancy in addition to the primary, excluding low-risk neoplasms as determined by the Investigator (e.g., non-metastatic basal cell or squamous cell skin carcinoma) and other indolent malignancies will be allowed after discussion with the Sponsor).
9. Has a history of or active infection with HIV 1 or 2, a history of or active infection with HBV based upon HBV antigenemia or viral load, or positive read for hepatitis C virus (\[HCV\] viral load \>15 IU/mL) at Screening. 10. Has a history of known genetic predisposition to HLH/MAS.
11\. Has undergone splenectomy, has an active chronic liver disease, Wilson's disease, hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, genetic hemochromatosis, history of or planned liver transplant for end-stage liver disease of any etiology, documented history of advanced liver fibrosis or history of cirrhosis and/or hepatic decompensation including ascites requiring paracentesis rather than medical therapy, modified Child-Pugh B or C, clinically relevant hepatic encephalopathy within the preceding 6 months, or variceal bleeding. 12. Has received a vaccine within 14 days of W1D1 13. Has active autoimmune disease. 14. Has a history of significant CNS disease, such as stroke (past history of transient ischemic attacks more than 3 months ago and controlled is allowed) or uncontrolled and unstable epilepsy. 15. Has severe pulmonary interstitial disease and/or oxygen saturation on room air \< 92%. 16. Baseline Q-T correlated (QTc) interval of \> 470 msec for females and \> 450 msec for males calculated using Fridericia's formula. 17. New York Heart Association Class III or IV cardiac disease, or myocardial ischemia or infarction within 180 days of Screening, vaso-vagal sensitivity, unstable angina, coronary/peripheral artery bypass graft, worsening/ decompensated heart failure within the past 6 months, or any other clinically significant cardiac abnormality that, in the judgement of the Investigator, would pose a health risk to the subject. 18. Major surgical procedure within 4 weeks prior to first dose of Decoy20, or anticipation of need for a major surgical procedure, during the study. 19. Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or Decoy20 administration. 20. Has received investigational therapy within 28 days or 5 half-lives of the start of study drug. 21. Unwillingness or inability to comply with procedures required in this protocol. 22. Known allergy or hypersensitivity to Decoy20 or one of the ingredients of Decoy20. 23. For Part 2c, participants with ongoing immune-related adverse events (irAEs) from other agents or who required permanent discontinuation of prior ICIs due to irAEs. Participants with a prior history of Grade 3 or higher irAE except for those with a history of an immune-related endocrinopathy which is currently treated and clinically stable. Participants with a history of (non-infectious) Grade 2 or higher pneumonitis that required steroids.
