This study is an open-label, phase 1/1b study of the pressure-enabled hepatic artery infusion
of SD-101, a TLR 9 agonist, alone or in combination with intravenous checkpoint blockade in
adults with metastatic uveal melanoma.
In the Sentinel Cohort, patients will receive 2 SD-101 infusions (2 weeks apart) with
assessments for toxicity prior to escalating from the first dose level (0.5 mg) to the second
dose level (2 mg). In the absence of dose-limiting toxicities (DLTs), each patient will be
eligible to transition into Cohort A.
In Cohorts A-C and Phase 1b, patients will receive 2 cycles of SD-101. Each cycle consists of
3 consecutive weekly infusions. Escalating doses of SD-101 will be administered alone (Cohort
A), together with nivolumab (Cohort B), and together with combined ipilimumab and nivolumab
(Cohort C). Cohorts B and C will begin one dose level below the MTD or optimal dose from
Cohort A to optimize safety when adding CPI to SD-101.
Following determination of the recommended MTD or optimal dose of SD-101 for PEDD/HAI and
which checkpoint inhibitor (CPI) regimen(s) are tolerated, the study will progress to Phase
1b. Patients in Phase 1b will receive the SD-101 dose selected from Phase 1 in the presence
of systemic single- or double-agent checkpoint blockade. The choice of single- or
double-agent CPI therapy together with SD-101 for Phase 1b will consider safety data in
addition to response rates from Cohorts B and C in Phase 1.
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
3. Has histologically or cytologically confirmed metastatic UM with liver-only or liver
dominant disease. Liver-dominant disease will be defined as:
1. Phase 1, Cohort A - Intrahepatic metastases representing the largest fraction of
disease relative to other organs, with permissible extrahepatic sites being the
lungs, skin or subcutaneous tissues, and bone.
2. Phase 1, Cohorts B and C and Phase 1b - Intrahepatic metastases representing the
largest fraction of disease relative to other organs, or if progression of LM
represent a significant threat to the patient's life.
4. Has not received prior cytotoxic chemotherapy, targeted therapy, or external radiation
therapy within 14 days prior to enrollment
5. Phase 1 only: Has not received therapy with prior immunological checkpoint blockade
within 30 days before the first dose of study intervention and has no ongoing
immune-mediated AEs Grade 2 or higher Phase 1b only: Has not ever received therapy
with prior immunological checkpoint blockade
6. Has not ever received prior embolic HAI therapy with permanent embolic material.
Note: 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.
7. Has no prior history of or other concurrent malignancy unless the malignancy is
clinically insignificant, no ongoing treatment is required, and the patient is
8. Has measurable disease in the liver according to RECIST v.1.1 criteria
9. Has an ECOG PS of 0-1 at screening
10. Has a life expectancy of >3 months at screening as estimated by the investigator
11. Has a QTc interval ≤480 msec
12. 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).
13. Has adequate organ function at screening as evidence 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.
14. 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 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
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 only:
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, 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
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
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