| Eligibility |
Inclusion Criteria:
1. Have histologically confirmed evidence of HCC, Childs-Pugh score of =7.
a. Participants must be willing to provide specimen from fresh, pre- and on-treatment
tumor core biopsies for histologic diagnosis and translational studies.
2. Radiographically measurable disease by RECIST1.1 in at least one site.
3. Deemed to not be a candidate for resection or other local-regional therapy.
4. Must not be receiving treatment with other investigational agents and must not have
received any other systemic therapy prior to registration.
a. Prior radioembolization, local ablative therapies (radiofrequency, microwave or
cryoablation), radiation (external beam or stereotactic), or hepatic resection
permitted if completed = 4 weeks prior to study enrollment and if patient has
recovered with = grade 1 toxicity and if untreated measurable disease is present.
5. Be willing and able to provide written informed consent/assent for the trial.
6. Participants must be = 18 years
7. Have a Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
8. If hepatitis B is present, participants must be on anti-viral HBV therapy.
9. All women of childbearing potential (not surgically sterilized and between menarche
and 1 year post menopause) must have a blood test to rule out pregnancy within 24
hours prior to start of study treatment
10. All women of childbearing potential must agree to follow instructions for method(s) of
contraception for the duration of treatment with study treatment (s) and for 5 months
following discontinuation of study treatment.
11. Males who are sexually active with women of childbearing potential must agree to
follow instructions for method (s) of contraception for the duration of treatment with
study treatment and for 7 months following discontinuation of study treatment.
Additionally, male participants must not donate sperm during this period.
12. Demonstrate adequate organ function as defined by the following required lab and
acceptable range criteria:
Adequate bone marrow function:
Absolute neutrophil count > 1000/mcL Platelet count > 50,000/mcL Hemoglobin > 8.5 g/dL
Adequate hepatic function:
Total bilirubin < 2 mg/dL or < 1.5 times upper limit of normal (ULN) AST and ALT < 5 times
ULN INR < 1.5 times ULN Albumin > 2.8 g/dL
Adequate renal function:
Creatinine < 2.0 mg/Dl
Exclusion Criteria:
1. Women who are pregnant or breastfeeding.
2. Presence of other malignancies. Participants with active second malignancy other than
non-melanoma skin cancer or cervical carcinoma in situ. NOTE: Patients with history of
malignancy are not considered to have a "currently active" malignancy if they have
completed therapy and are now considered by their physician to be at less than 30%
risk for relapse.
3. Have active or history of Tuberculosis
4. Participants with known HIV positive status
5. Participants with known CNS metastases
6. Uncontrolled ascites
7. Uncontrolled encephalopathy
8. Uncontrolled gastro-esophageal varicesPrior organ allograft or allogeneic bone marrow
transplantation
9. Participants with active, known, or suspected autoimmune disease. Participants with
vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
condition only requiring hormone replacement, euthyroid participants with a history of
Grave's disease (participants with suspected autoimmune thyroid disorders must be
negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating
immunoglobulin prior to first dose of study treatment), psoriasis not requiring
systemic treatment, or conditions not expected to recur in the absence of an external
trigger are permitted to enroll.
10. Participants with a condition requiring systemic treatment with either corticosteroids
(> 10 mg daily prednisone equivalents) or other immunosuppressive medications within
14 days of study treatment administration except for adrenal replacement steroid doses
> 10 mg daily prednisone equivalent in the absence of active autoimmune disease. Note:
Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating
study treatment is permitted.
11. Interstitial lung disease that is symptomatic or may interfere with the detection or
management of suspected treatment-related pulmonary toxicity.
12. Uncontrolled or significant cardiovascular disease including, but not limited to, any
of the following:
- Myocardial infarction or stroke/transient ischemic attack within the past 6
months
- Uncontrolled angina within the past 3 months
- Any history of clinically significant arrhythmias (such as ventricular
tachycardia, ventricular fibrillation, or torsades de pointes)
- History of other clinically significant heart disease (eg, cardiomyopathy,
congestive heart failure with New York Heart Association functional
classification III to IV, pericarditis, significant pericardial effusion, or
myocarditis)
- Cardiovascular disease-related requirement for daily supplemental oxygen therapy.
13. Participants with ongoing or active, uncontrolled infections (afebrile for = 48 hours
off antibiotics). If hepatitis B is present, must be on anti-viral HBV therapy.
14. Must not have a psychiatric illness, other significant medical illness, or social
situation which, in the investigator's opinion, would limit compliance or ability to
comply with study requirements.
15. Any major surgery within 4 weeks of study treatment. Participants must have recovered
from the effects of major surgery or significant traumatic injury at least 14 days
before
16. Any uncontrolled inflammatory disease including Crohn's disease and ulcerative colitis
17. Treatment with botanical preparations (eg, herbal supplements, including potential
drugs of abuse, or traditional Chinese medicines) intended for general health support
or to treat the disease under study within 2 weeks prior to randomization/treatment.
18. Concomitant use of statins while on study.
19. Current or history of clinically significant muscle disorders (eg, myositis), recent
unresolved muscle injury, or any condition known to elevate serum CK levels.
20. Known history of sensitivity to infusions containing Tween 20 (polysorbate 20) and
Tween 80 (polysorbate 80).
21. Participants who have received a live / attenuated vaccine within 30 days of first
treatment.
22. Concomitant use of any live / attenuated vaccine during treatment and until 100 days
following last dose.
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