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


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Trial ID: NCT04935229


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.

Official Title

A Phase 1/1b, Open-Label Study of the Pressure-Enabled Hepatic Artery Infusion of SD-101, a TLR9 Agonist, Alone or in Combination With Intravenous 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

   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

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


drug: SD-101

biological: Nivolumab

biological: Ipilimumab


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Phuong Pham