This is a single-arm Phase II trial of pembrolizumab in patients with hepatitis B
virus-related hepatocellular carcinoma with parallel study on baseline and serial change in
the immune environment.
Subjects should have a confirmed diagnosis of HCC (in accordance with the AASLD guideline)
and confirmed chronic infection with hepatitis B virus as defined by positivity 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. They must have disease not amenable to a
curative treatment approach or loco-ablation. Subject must be fit and agreeable with baseline
and post-treatment biopsy of tumor. Subjects must have at least one measurable lesion per
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an Eastern Cooperative Oncology
Group (ECOG) performance score of 0 or 1 and adequate organ functions. 30 subjects will be
enrolled to receive pembrolizumab 200 mg IV every 3 weeks(Q3W). Pre-treatment and
on-treatment biopsy after 2 cycles of Pembrolizumab will be preformed. Treatment will be
stopped when progression of disease or intolerable toxicity occurs. The primary objectives of
this trial are to study the efficacy and safety of pembrolizumab in patients with HBV-related
HCC and to study the serial change in RNA expression of immune-related gene panel in
post-treatment biopsy tissue.
The secondary objectives of this trial are to study the serial change in cytokine profile
between pre-treatment and post-treatment samples, to study the PD-L1 immunohistochemical
(IHC) expression in tumor sample at baseline and post-treatment tissue samples and to study
the presence of tumor infiltrating lymphocytes in the baseline and post-treatment tumor
samples.
The exploratory objective of this trial is to evaluate the possibility of using baseline and
the serial change in RNA expression of immune-related gene panel or PD-L1/2 IHC to predict
treatment response.