Pembrolizumab (MK-3475) in Hepatocellular Carcinoma

Inclusion Criteria

• FOR ARM 1 AND 2: Subjects with advanced hepatocellular carcinoma (HCC) with no curative option; for Arm 2 subjects that are HCV-positive with genotype 1 or 4 virus infection will be enrolled
• Be willing and able to provide written informed consent for the trial; the subject may also provide consent for Future Biomedical Research (FBR); however, the subject may participate in the main trial without participating in FBR.
• Have histologically or cytologically documented HCC (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects is required; for subjects without cirrhosis histological confirmation is mandatory
• FOR ARM A AND B: Have Barcelona Clinic Liver Cancer (BCLC) stage C disease or BCLC stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
• Have a Child-Pugh A liver score at screening or within 14 days of first dose of study drug
• Have a predicted life expectancy of greater than 3 months
• Have measurable disease based on RECIST 1.1 as confirmed by the blinded MD Anderson radiology; target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions; Note: the same image acquisition and processing parameters should be used throughout the study for a given subject
• Have a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) performance scale within 7 days of first dose of study drug
• Have documented objective radiographic progression after stopping treatment with sorafenib or else intolerance to sorafenib; intolerance to sorafenib is defined as: Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 drug-related adverse event(s) which both a) persisted in spite of comprehensive supportive therapy according to institutional standards and b) persisted or recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose level; patients treated on sorafenib as the last treatment may start pembrolizumab at least 14 days after the last dose of sorafenib
• FOR ARM B: Subjects with chronic infection by HCV who are treated or untreated are allowed on study; subjects with a past or resolved hepatitis B virus (HBV) infection, defined as having a negative hepatitis B surface antigen (HBsAg) test and a positive total hepatitis B core antibody (HBcAb) test and negative HBV deoxyribonucleic acid (DNA) test at screening, are eligible for the study
• Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication (cycle 1, day 1) (female subjects of childbearing potential); if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Be willing to use an adequate method of contraception for the course of the study through 120 days (Arm A) or 180 days (Arm B) after the last dose of study medication (male and female subjects of childbearing potential; acceptable methods of contraception are as follows: A) single method (one of the following is acceptable): a) intrauterine device (IUD); b) vasectomy of a female subject's male partner; c) contraceptive rod implanted into the skin B) combination method (requires use of two of the following): a) diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide); c) cervical cap with spermicide (nulliparous women only); d) contraceptive sponge (nulliparous women only); e) male condom or female condom (cannot be used together); f) hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous contraceptive injection; abstinence (relative to heterosexual activity) can be used a