Sorafenib Tosylate and Pembrolizumab in Treating Patients With Advanced or Metastatic Liver Cancer
Sorafenib Tosylate and Pembrolizumab in Treating Patients With Advanced or Metastatic Liver Cancer
This phase Ib/II trial studies how well sorafenib tosylate and pembrolizumab work in treating
 patients with liver cancer that has spread to other parts of the body. Sorafenib tosylate may
 stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
 Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells
 to grow and spread. Giving sorafenib tosylate and pembrolizumab may work better in treating
 patients with liver cancer.
PRIMARY OBJECTIVES:

 I. To assess the overall response rate (ORR) related to the combination of sorafenib tosylate
 (sorafenib) + pembrolizumab in advanced hepatocellular carcinoma patients.

 SECONDARY OBJECTIVES:

 I. To assess time to tumor progression in patients who received the combination therapy of
 sorafenib + pembrolizumab compared to historical data on sorafenib only treatment in patients
 with advanced hepatocellular carcinoma.

 TERTIARY OBJECTIVES:

 I. To obtain data on changes in immune cell function and in the tumor microenvironment pre-
 and post-treatment to screen for potential biomarkers that may be able to predict clinical
 benefit.

 - All patients will be followed for survival

 OUTLINE:

 Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days -28 to -1 and 1-21.
 Patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses
 repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

 After completion of study treatment, patients are followed up at 30 days, every 3 months for
 up to 1 year, then every 6 months thereafter.
Inclusion Criteria:

 -  Participant must have histologically or radiographically confirmed hepatocellular
 cancer (HCC) that is advanced or metastatic and if archival tissue is available, have
 archival tissue submitted for PD-L1, PD-L2 testing

 -  Participants with measurable disease that has progressed are eligible if prior surgery
 or locoregional therapy occurred > 28 days prior to enrollment

 -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky
 >= 60%)

 -  Child-Pugh class-A liver function

 -  Absolute neutrophil count (ANC) >= 1,500/ mcL

 -  Hemoglobin >= 8.5 g/dL

 -  Platelets >= 75,000/ mcL

 -  Total bilirubin =< 2.0 mg/dL

 -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 X ULN

 -  Serum Creatinine <= 1.5 upper limit of normal (ULN)or Creatinine clearance > 50
 mL/minute if serum creatinine is elevated above 1.5 X ULN

 -  Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
 criteria present

 -  Ability to swallow and retain oral medication

 -  Participants of child-bearing potential must agree to use adequate contraceptive
 methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study
 entry; should a woman become pregnant or suspect she is pregnant while she or her
 partner is participating in this study, she should inform her treating physician
 immediately

 -  Participant or legal representative must understand the investigational nature of this
 study and sign an Independent Ethics Committee/Institutional Review Board approved
 written informed consent form prior to receiving any study related procedure

 -  Participants with past or ongoing hepatitis C virus (HCV) infection will be eligible
 for the study. The treated participants must have completed their treatment at least 1
 month prior to starting study intervention.

 -  Participants with controlled hepatitis B will be eligible as long as they meet the
 following criteria:

 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. Participants on active HBV therapy
 with viral loads under 100 IU/mL should stay on the same therapy throughout study treatment
 Participants who are anti-HBc , negative for Hepatitis B surface antigen (HBsAg) and
 negative or positive for anti-HBs, and who have an HBV viral load under 100 IU/mL , do not
 require HBV anti-viral prophylaxis

 Exclusion Criteria:

 -  One prior line of therapy that may include a PDL1 blocker allowed, no prior sorafenib
 or PD1 blocker allowed.

 -  Participants who have had radiotherapy or chemotherapy within 4 weeks (6 weeks for
 nitrosoureas or mitomycin C) prior to entering the study or those who have not
 recovered from adverse events due to agents administered more than 4 weeks earlier

 -  Any evidence of bleeding diathesis (patients on therapeutic warfarin or heparin will
 be excluded)

 -  Participants with a history of variceal bleed within 6 months prior to enrollment

 -  Known human immunodeficiency virus (HIV)-positive participants (even if on combination
 retrovirals, participant will be excluded

 -  Participants with chronic autoimmune disease

 -  Participants with known brain metastases should be excluded from this clinical trial

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
 arrhythmia, or psychiatric illness/social situations that would limit compliance with
 study requirements

 -  Has known history of, or any evidence of active, non-infectious pneumonitis

 -  Pregnant or nursing female participants

 -  Unwilling or unable to follow protocol requirements

 -  Any condition which in the Investigator's opinion deems the participant an unsuitable
 candidate to receive study drug

 -  Received a live vaccine within 30 days prior to start of study treatment