Pembrolizumab in Advanced Hepatocellular Carcinoma as Second-line Treatment After Failure of Sorafenib
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Pembrolizumab
Intervention description: Pembrolizumab (MK-3475) 200 mg every 3 weeks (Q3W)
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Pembrolizumab (MK-3475) 200 mg every 3 weeks (Q3W)
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      This is a single-arm, single-center, open-label trial of pembrolizumab (MK-3475) in subjects
      with advanced hepatocellular carcinoma as second-line treatment after failure of sorafenib.

      Approximately 60 subjects will be enrollment to evaluate the efficacy and safety of
      pembrolizumab.

      Enrollment will begin with all subjects without regard for PD-L1 expression status.

      An evaluable specimen for PD-L1 status must be available and confirmed prior to enrollment.

      All study subjects will be evaluated every 6 weeks (+/- 7 days) following the date of IP drug
      adminstration for the first 12 months and every 12 weeks (+/- 7 days) thereafter until
      progression of disease is documented with radiologic imaging (computed tomography or magnetic
      resonance imaging).

      The primary efficacy endpoint is ORR (objective response rate) per RECIST 1.1.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be willing and able to provide written informed consent/assent for the trial. The
             subject may also provide consent for Biomedical Research. However, the subject may
             participate in the main trial without participating in Biomedical Research.

          2. Have histologically or cytologically confirmed diagnosis of HCC (fibrolamellar and
             mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) based on pathology
             report.

          3. 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.

          4. Have a Child-Pugh class A liver score

          5. Has experienced documented objective radiographic or clinical disease progression
             during first-line sorafenib therapy.

          6. Have measurable disease based on RECIST1.1 as determined by investigator.

          7. Be willing to provide fresh tissue for biomarker analysis, and, based on the adequacy
             of the tissue sample quality for assessment of biomarker status. Repeat samples may be
             required if adequate tissue is not provided. Newly obtained endoscopic biopsy
             specimens are preferred to archived samples and formalin-fixed, paraffin-embedded
             (FFPE) block specimens are preferred to slides.

        Exclusion Criteria:

          1. Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment.

          2. Has received sorafenib within 14 days of first dose of study medication.

          3. Has had esophageal or gastric variceal bleeding within the last 6 months. All subjects
             will be screened for esophageal varices, unless such screening has been performed in
             the past 12 months before first dose of treatment. If varices are present, they should
             be treated according to institutional standards before starting study treatment.

          4. Had a solid organ transplant.

          5. Has active autoimmune disease that has required systemic treatment in 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.

          6. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          7. Has received locoregional therapy to liver (transcatheter chemoembolization [TACE],
             transcatheter embolization [TAE], radiation, radioembolization, or ablation) or major
             surgery to liver or other site within 4 weeks prior to the first dose of study drug.
             Minor surgery (e.g., simple excision, tooth extraction) must have occurred at least 7
             days prior to the first dose of study treatment (Cycle 1, Day 1).