Durvalumab for Advanced Hepatocellular Carcinoma in Patients With Active Chronic Hepatitis B Virus Infection

  • End date
    Dec 31, 2023
  • participants needed
  • sponsor
    National Taiwan University Hospital
Updated on 24 November 2021


PD1 blockade has been approved as salvage therapy for advanced hepatocellular carcinoma (HCC). Although there is not solid evidence that PD1 blockade would induce hepatitis B virus (HBV) reactivation, previous clinical trials of PD1 blockade required enrolled patients to receive anti-HBV medications and control the viral load to be under 100-2000 IU/mL before initiation of PD1 blockade therapy. Such a requirement may not be necessary and could delay the treatment. Guidelines for prevention of chemotherapy induced HBV reactivation only suggest combining anti-HBV medications during the chemotherapy course without such a requirement of very load HBV viral load.

The investigators hypothesized that under anti-HBV medications, patients with advanced HCC and active chronic hepatitis B virus (HBV) infection can receive durvalumab treatment without increased risks of HBV reactivation and related complications.


Although durvalumab has not been approved as treatment for HCC, similar PD1 blockade agents such as nivolumab and pembrolizumab have gain approval as salvage therapy for advanced HCC. The investigators will enroll 43 patients with active (defined as serum viral load > 2000 IU/mL) chronic HBV infection (defined as positive serum HBV surface antigen). All patients would receive entecavir within 7 days of initiation of durvalumab treatment. Durvalumab 1500 mg would be given intravenously every 4 weeks until confirmed disease progression, intolerable side effects, or completion of 24 treatment. Tumor assessment will be performed every 8-12 weeks. HBV viral load will be monitored at least once per month. Entecavir treatment will be continued at least 6 months after discontinuation of durvalumab treatment.

Condition Advanced Hepatocellular Carcinoma
Treatment durvalumab
Clinical Study IdentifierNCT04294498
SponsorNational Taiwan University Hospital
Last Modified on24 November 2021


Yes No Not Sure

Inclusion Criteria

Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc])
Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection (except HBV infection), symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
History of another primary malignancy except for
Malignancy treated with curative intent and with no known active disease 5 years before the first dose of IP and of low potential risk for recurrence
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Adequately treated carcinoma in situ without evidence of disease
History of leptomeningeal carcinomatosis
Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry
History of active primary immunodeficiency or HIV infection
Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), and hepatitis C
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab
Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment

Exclusion Criteria

Serum HBeAg (+)
Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
Active or prior documented GI variceal bleed or history of upper GI bleeding, ulcers, or esophageal varices with bleeding within 12 months; adequate endoscopic therapy according to institutional standards is required for patients with history of esophageal variceal bleeding or assessed as high risk for esophageal variceal by the treating investigator
Previous organ transplants
Participation in another clinical study with an investigational product during the last 2 weeks
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) 14 days prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by the principal investigator
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