Intrahepatic Delivery of SD-101 by Pressure-Enabled Regional Immuno-oncology (PERIO), With Checkpoint Blockade in Adults With Metastatic Uveal Melanoma

Inclusion Criteria: 1. Male or female, age ≥18 years of age at screening 2. Able to understand the study and provide written informed consent prior to any study procedures 3. Has histologically or cytologically confirmed metastatic UM with liver-only or liver dominant disease. Liver-dominant disease will be defined as intrahepatic metastases representing the largest fraction of disease relative to other organs. 4. Has not received prior cytotoxic chemotherapy, targeted therapy, or external radiation therapy within 14 days prior to screening 5. Has not received therapy with prior immunological checkpoint blockade within 21 days before the first dose of study intervention and has no ongoing immune-mediated AEs Grade 2 or higher 6. Has not ever received prior embolic HAI therapy with permanent embolic material Note: Previous embolic HAI therapy with permanent embolic material will not be exclusionary if following this therapy, the target vessels are not occluded and the liver segments containing target tumors are perfused based on the patient's screening CT/MRI. 7. Prior surgical resection or radiofrequency ablation of oligometastatic liver disease is allowed on both the Phase 1 and Phase 1b portions of this study. Liver lesions that received ablative therapies should not be considered target lesions unless they have clearly progressed since the therapy. 8. Has no prior history of or other concurrent malignancy unless the malignancy is clinically insignificant, no ongoing treatment is required, and the patient is clinically stable 9. Has measurable disease in the liver according to RECIST v.1.1 criteria 10. Has an ECOG PS of 0-1 at screening 11. Has a life expectancy of \>3 months at screening as estimated by the investigator 12. Has a QTc interval ≤480 msec 13. All associated clinically significant (in the judgment of the investigator) drug-related toxicity from previous cancer therapy must be resolved (to Grade ≤1 or the patient's pretreatment level) prior to study treatment administration (Grade 2 alopecia and endocrinopathies controlled on replacement therapy are allowed) 14. Has adequate organ function at screening as evidenced by: * Platelet count \>100,000/μL * Hemoglobin ≥8.0 g/dL * White blood cell count (WBC) \>2,000/μL * Serum creatinine ≤2.0 mg/dL unless the measured creatinine clearance is ≥30 mL/min calculated by Cockcroft-Gault formula. * Total and direct bilirubin ≤2.0 × the upper limit of normal (ULN) and alkaline phosphatase ≤5 × ULN. For patients with documented Gilbert's disease, total bilirubin up to 3.0 mg/dL is allowed. * ALT and AST ≤5 × ULN * Prothrombin time/International Normalized Ratio (INR) or activated partial thromboplastin time (aPTT) test results at screening ≤1.5 × ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose for at least 4 weeks prior to the first dose of study intervention) Note: Laboratory tests with exclusionary results judged by the investigator as not compatible with the patient's clinical status may be repeated once for eligibility purposes. 15. Females of childbearing potential must be nonpregnant and nonlactating, or post-menopausal, and have a negative serum human chorionic gonadotropin (hCG) pregnancy test result at screening and a negative urine or serum pregnancy test prior to the first dose of study intervention. * Females of childbearing potential must agree to abstain from sexual activity with nonsterilized male partners, or if sexually active with a nonsterilized male partner must agree to use highly effective methods of contraception from screening, throughout the study and agree to continue using such precautions for 100 days after the final dose of study intervention. * Nonsterilized males who are sexually active with a female of childbearing potential must agree to use effective methods of contraception and avoid sperm donation from Day 1, throughout the study, and for 30 days after the final dose of study intervention. Exclusion Criteria: 1. Has received chemotherapy or an investigational agent within 14 days (or 5 half-lives, whichever is shorter) before screening 2. Has active, untreated brain metastasis 3. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. 4. Has portal vein thrombosis, or severe portal hypertension as defined by a history of variceal hemorrhage or active ascites accumulation 5. Has more than 2/3 parenchymal replacement by tumor of both liver lobes 6. Phase 1 and Phase 1b: 1. Has Child-Pugh Class B or C cirrhosis, or 2. Has experienced a Grade 3 or higher immune-related AE from prior CPI therapy that has not recovered to Grade 1 for a minimum of 14 days prior to administration of SD-101 or CPI, or 3. Is unable to be temporarily removed from chronic anticoagulation therapy, or 4. Has a history of bleeding disorders 7. Has active coronavirus disease 2019 (COVID-19), other severe infection, including a liver infection, within 2 weeks before the first dose of study drug, or uncontrolled human immunodeficiency virus (HIV) infection at screening 8. Has had bacterial pneumonia within 8 weeks of first dose of study drug 9. Has active, known, or suspected autoimmune disease or immune-mediated disease. Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment or conditions not expected to recur in the absences of an external trigger are not exclusionary. 10. Is receiving systemic steroid therapy \>10 mg of prednisone daily or equivalent or any other immunosuppressive medication at any dose level. Local steroid therapies (e.g., otic, ophthalmic, intra-articular or inhaled medications) are acceptable. 11. Has significant concurrent or intercurrent illness, psychiatric disorder, or alcohol or chemical dependence that would, in the opinion of the Investigator and/or Medical Monitor, compromise their safety or compliance or interfere with interpretation of the study 12. Lactating women are excluded from study participation 13. Has previously received SD-101 14. Medical history of significant hypersensitivity, severe and unresolved immune-mediated reactions, severe infusion-related reactions, or allergic reaction to TLR9 agonists or CPI agents in the judgment of the investigator 15. Patients who were enrolled in the Phase 1 portion of the study will not be eligible for enrollment in Phase 1b