Sorafenib Tosylate and Pembrolizumab in Treating Patients With Advanced or Metastatic 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 confirmed hepatocellular cancer (HCC) that is
advanced or metastatic and have archival tissue available 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

- Serum 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:

- Participants who have received prior sorafenib or anti-PD1 therapy for HCC

- 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