| Eligibility |
Inclusion Criteria:
1. Confirmed diagnosis of advanced hepatocellular carcinoma (in accordance with the AASLD
guidelines)
2. Confirmed chronic infection with hepatitis B virus as defined by positivity for HBsAg
3. For patients who are positive for HBsAg, antiviral therapy for HBV must be given for
at least 12 weeks and HBV viral load must be less than 100 IU/mL prior to first dose
of study drug. Subjects on active HBV therapy with viral loads under 100 IU/ml should
stay on the same therapy throughout study treatment.
4. Disease extent is not amenable to curative surgery or loco-ablation
5. Patients who are fit and agreeable with baseline and post-treatment biopsy of tumor
Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
6. Be willing and able to provide written informed consent/assent for the trial.
7. Be = 18 years of age on day of signing informed consent.
8. Have measurable disease based on RECIST 1.1.
9. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples
cannot be provided (e.g. inaccessible or subject safety concern) may submit an
archived specimen only upon agreement from the Sponsor.
10. Have a performance status of 0 or 1 on the ECOG Performance Scale.
11. Demonstrate adequate organ function as defined, all screening labs should be performed
within 10 days of treatment initiation.
Adequate Organ Function Laboratory Values:
Hematological Absolute neutrophil count (ANC) =1,200 /mcL Platelets =75,000 / mcL
Hemoglobin =8g/dL without transfusion or EPO dependency (within 7 days of assessment)
Renal Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also
be used in place of creatinine or CrCl) =1.5 X upper limit of normal (ULN) OR =60
mL/min for subject with creatinine levels > 1.5 X institutional ULN Hepatic Serum
total bilirubin = 2mg/dL, or direct bilirubin=ULN for those with total bilirubin >
2mg/dL or Direct bilirubin = ULN for subjects with total bilirubin levels > 1.5 ULN
AST (SGOT) and ALT (SGPT) = 5 X ULN Albumin >3.0 mg/dL Coagulation International
Normalized Ratio (INR) or Prothrombin Time (PT) orActivated Partial Thromboplastin
Time (aPTT) =1.5 X ULN Creatinine clearance should be calculated per institutional
standard.
12. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.
13. Female subjects of childbearing potential (Section 5.7.2) must be willing to use an
adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the
course of the study through 120 days after the last dose of study medication.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
14. Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate
method of contraception as outlined in Section 5.7.1- Contraception, starting with the
first dose of study therapy through 120 days after the last dose of study therapy.
Exclusion Criteria:
1. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapyor used an investigational
device within 4 weeks of the first dose of treatment.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment.
3. Has a known history of active TB (Bacillus Tuberculosis)
4. Hypersensitivity to pembrolizumab or any of its excipients.
5. Had a solid organ or hematologic transplant
6. Has had esophageal or gastric variceal bleeding within the last 6 months. All subjects
will be screened for esophageal varices, unless such screening has been performed in
the past 12 months before first dose of treatment. If varices are present, they should
be treated according to institutional standards before starting trial treatment
7. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events
due to agents administered more than 4 weeks earlier.
8. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at
baseline) from adverse events due to a previously administered agent.
- Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and
may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting
therapy.
9. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include cancer-insitu with curative treatment or malignancy more than 3
years prior to enrollment.
10. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging for at least four weeks
prior to the first dose of trial treatment and any neurologic symptoms have returned
to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability.
11. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
12. Has known history of, or any evidence of active, non-infectious pneumonitis.
13. Has an active infection requiring systemic therapy.
14. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
15. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
16. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.
17. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
18. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
19. Has untreated active Hepatitis B Note: To qualify for enrollment, antiviral therapy
for HBV must be given for at least 3 months, and HBV viral load must be less than 100
IU/mL prior to first dose of study drug. Those on active HBV therapy with viral loads
under 100 IU/mL should stay on the same therapy throughout trial treatment. Those
subjects who are anti-HBc (+), and negative for HBsAg, and negative for anti-HBs, and
have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis, but
need close monitoring.
20. Baseline HBV DNA level > 100 IU/ml
21. Patients with concomitant HCV infection (as evidenced by Anti-HCV positivity)
22. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.
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