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

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.

What this study is about