Pembrolizumab (Keytruda) in Advanced Hepatocellular Carcinoma

Inclusion Criteria

• Patients must have diagnosis of advanced hepatocellular cancer (HCC) by one of the following:
• Histopathology
• Elevated serum alpha-fetoprotein (AFP) >400 ng/ml and findings on magnetic resonance imaging (MRI) or computed tomography (CT) scans characteristic of HCC
• Findings on triple phase MRI or CT scans characteristic of HCC in patients with cirrhosis and tumors at least 1 cm or greater, without a curative treatment option (transplant, resection, or ablation).
• Measurable disease as defined by RECIST v1.1 (provided in Section 14.0).
• Radiographic progression on previously treated areas (as defined by RECIST v1.1).
• Subject refusal for sorafenib treatment or intolerance to sorafenib are also allowed (intolerance is defined as ≥ 28 days of sorafenib (not necessarily consecutive) or ≥grade 3 toxicity due to sorafenib which does not resolve with appropriate supportive care).
• Patients should have failed at least one prior systemic therapy regimen which could include sorafenib. Patients may have progressed on sorafenib, been intolerant of, or refused sorafenib. Patients who are documented to refuse systemic chemotherapy or sorafenib are also eligible. No limit to prior systemic therapy. Prior locoregional therapy such as surgery, radiofrequency ablation or transarterial chemoembolization are also allowed, provided that progression has been documented after these therapies, and ≥4 weeks have elapsed since the last therapy; (these will not be counted as systemic therapy).
• Child-Pugh Classification with score ≤ 7 points. See Appendix G for criteria.
• Age ≥ 18 years
• Estimated life expectancy, in the judgement of the Investigator, of at least ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. See Appendix C.
• Adequate bone marrow function as defined below:
• absolute neutrophil count (ANC) ≥ 1.2 x 10^9/L,
• platelets (PLT) ≥ 50 x 10^9/L
• Adequate liver function as defined below:
• serum bilirubin 1.5 x ULN.
• Suitable venous access to allow for all study-related blood sampling.
• Female subject of childbearing potential (CBP) must have a negative urine or serum pregnancy within 3 days prior to receiving the first dose of study medication.
• Females of child bearing potential that are sexually active must agree to either practice 2 medically accepted highly effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 120 days after the last dose of study drug. See Appendix H for protocol-approved highly effective methods of contraceptive combinations. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
• Negative test for pregnancy is required of females of child-bearing potential; A female of child bearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
• has not undergone a hysterectomy or bilateral oophorectomy; or
• has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months or 730 days).
• Conception while on treatment must be avoided
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

• 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Diagnosis of immunode