| Eligibility |
Inclusion Criteria:
1. 18 years of age or older with locally advanced, metastatic or unresectable
hepatocellular carcinoma or intrahepatic cholangiocarcinoma, with the diagnosis
confirmed by radiologic, histologic or cytologic analysis or clinical features
according to the American Association for the Study of Liver Diseases.
2. Previously received 1 line of standard therapy for liver cancer and with persistent or
progressive measurable disease, as defined by RECIST version 1.1, that is not amenable
to curative therapies
3. Performance status score of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
scale (scores range from 0 to 5, with higher numbers reflecting greater disability)
4. Designation of class A to B7 on the Child-Pugh liver function scale (a three-category
scale [A, B, or C], with C indicating the most severe compromise of liver function)
5. Adequate hematologic and organ function.
6. Has radiographically, histologically or cytologically confirmed HCC or ICC with
liver-only or liver-dominant disease. Liver-dominant will be defined as intrahepatic
disease representing the largest fraction of disease.
7. Able to understand the study and provide written informed consent prior to any study
procedures
8. Has not received prior cytotoxic chemotherapy, targeted therapy, or external radiation
therapy within 14 days prior to C1D1
9. 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
tumors are perfused based on the patient's screening imaging.
Prior surgical resection or radiofrequency ablation of oligometastatic liver disease
is allowed. Liver lesions that received ablative therapies should not be considered
target lesions unless they have clearly progressed since the therapy or have viable
tumor on contrast enhanced MRI or CT.
10. 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
11. Has measurable disease in the liver according to RECIST v.1.1 criteria
12. Has a life expectancy of >3 months at screening as estimated by the investigator
13. Has a QTc interval =480 msec
14. 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).
15. Has adequate organ function at screening as evidenced by:
- Platelet count >80,000/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.
16. 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.
17. For patients with a documented FGFR2 mutation, prior treatment with a FGFR2-targeted
agent or refusal of treatment with at least one of these agents must be documented.
For patients with a documented IHD1 mutation, prior treatment with an IHD1 targeted
agent or refusal of treatment with ivosidenib must be documented.
Exclusion Criteria:
1. Has received chemotherapy or an investigational agent within 14 days (or 5 half-lives,
whichever is shorter) before C1D1.
2. Has active, untreated brain metastasis.
3. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
4. Has main portal vein thrombosis, or severe portal hypertension as defined by a history
of variceal hemorrhage or active ascites accumulation refractory to medical management
5. Has more than 2/3 parenchymal replacement by tumor of both liver lobes.
6. Has Child-Pugh Class B 8-9 or C cirrhosis.
7. Has experienced a Grade 3 or higher immune-related AE from prior CPI therapy.
Note: Patients who have experienced a Grade 3 immune-related AE from prior CPI therapy
will not be excluded if that AE has since recovered to a Grade 1 for a minimum of 14
days.
8. Is unable to be temporarily removed from chronic anticoagulation therapy.
9. Has a history of bleeding disorders.
10. 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.
11. 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 absence of an external trigger are not
exclusionary.
12. 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.
13. 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.
14. Lactating women are excluded from study participation.
15. Has previously received SD-101.
16. 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.
17. Patients who were enrolled in the Phase 1b portion of the study will not be eligible
for enrollment in Phase 2.
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