A Study of Durvalumab or Tremelimumab Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Advanced Hepatocellular Carcinoma
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02519348 |
Recruitment Status :
Active, not recruiting
First Posted : August 10, 2015
Last Update Posted : December 19, 2020
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Hepatocellular Carcinoma | Biological: Durvalumab + tremelimumab Biological: Durvalumab Biological: Tremelimumab Biological: Durvalumab + Bevacizumab | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 433 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Study of Safety, Tolerability, and Clinical Activity of Durvalumab and Tremelimumab Administered as Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Subjects With Advanced Hepatocellular Carcinoma |
Actual Study Start Date : | October 19, 2015 |
Actual Primary Completion Date : | November 6, 2020 |
Estimated Study Completion Date : | December 31, 2021 |

Arm | Intervention/treatment |
---|---|
Experimental: Durvalumab & Tremelimumab (Regimen 1)
Durvalumab in combination with Tremelimumab (Regimen 1)
|
Biological: Durvalumab + tremelimumab
Durvalumab will be administered by IV infusion in combination with tremelimumab. |
Experimental: Durvalumab
Durvalumab given as monotherapy
|
Biological: Durvalumab
Durvalumab will be administered by IV infusion. |
Experimental: Tremelimumab
Tremelimumab given as monotherapy
|
Biological: Tremelimumab
Tremelimumab will be administered by IV infusion. |
Experimental: Durvalumab & Tremelimumab (Regimen 2)
Durvalumab in combination with Tremelimumab (Regimen 2)
|
Biological: Durvalumab + tremelimumab
Durvalumab will be administered by IV infusion in combination with tremelimumab. |
Experimental: Durvalumab & Bevacizumab
Durvalumab in combination with Bevacizumab
|
Biological: Durvalumab + Bevacizumab
Durvalumab will be administered by IV infusion in combination with bevacizumab |
- Number of subjects reporting adverse events and number of subjects reporting serious adverse events. [ Time Frame: Screening through 3 months after the last dose of study medication ]
- Number of subjects experiencing dose limiting toxicities [ Time Frame: First dose of study medications through 4 weeks after the first dose of study medication ]
- Objective Response Rate [ Time Frame: Screening through 12 months after the last subject is randomized ]
- Duration of Response [ Time Frame: Screening through 12 months after the last subject is randomized ]
- Overall Survival [ Time Frame: Screening through 12 months after the last subject is randomized ]
- PD-L1 expression [ Time Frame: Screening through last dose of study medication ]
- Time to Progression [ Time Frame: From the date of first dosing to the first documentation of radiographic disease progression (per RECIST v1.1) ]
- Progression Free Survival [ Time Frame: Time from the date of first dosing to the first documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first ]
- Disease Control Rate [ Time Frame: Screening through 12 months after the last subject is randomized ]
- Time to Response [ Time Frame: Time from the first dose of investigational product to the first documentation of a subsequently confirmed objective response, assessed up to 24 months ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male or female subjects
- 18 years and older (Japan-20 years and older)
- Confirmed HCC based on histopathological findings from tumor tissues. Advanced HCC with diagnosis confirmed pathologically or with noninvasive methods.
- Immunotherapy-naïve
- Have either progressed on, are intolerant to, or refused treatment with sorafenib or another approved TKI. For arm 5 only: Have not received any prior systemic therapy for HCC.
Exclusion Criteria:
- Prior exposure to immune-mediated therapy
- Hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy
- GI Bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
- Ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose.
- Main portal vein thrombosis (Vp4) as documented on imaging
- Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment
- Active or prior documented autoimmune or inflammatory disease with some exceptions
- Current or prior use of immunosuppressive medication within 14 days with some exceptions

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02519348
United States, Arizona | |
Research Site | |
Phoenix, Arizona, United States, 85054 | |
United States, California | |
Research Site | |
San Francisco, California, United States, 94158 | |
United States, Connecticut | |
Research Site | |
New Haven, Connecticut, United States, 06510 | |
United States, Florida | |
Research Site | |
Jacksonville, Florida, United States, 32224 | |
Research Site | |
Tampa, Florida, United States, 33612 | |
United States, Indiana | |
Research Site | |
Indianapolis, Indiana, United States, 46202 | |
United States, Massachusetts | |
Research Site | |
Boston, Massachusetts, United States, 02114 | |
United States, New York | |
Research Site | |
New York, New York, United States, 10065 | |
Research Site | |
Stony Brook, New York, United States, 11794 | |
United States, North Carolina | |
Research Site | |
Durham, North Carolina, United States, 27705 | |
United States, Oregon | |
Research Site | |
Portland, Oregon, United States, 97213 | |
United States, Pennsylvania | |
Research Site | |
Philadelphia, Pennsylvania, United States, 19107 | |
Research Site | |
Philadelphia, Pennsylvania, United States, 19111 | |
United States, Tennessee | |
Research Site | |
Nashville, Tennessee, United States, 37203 | |
United States, Texas | |
Research Site | |
Dallas, Texas, United States, 75390 | |
United States, Washington | |
Research Site | |
Seattle, Washington, United States, 98109 | |
China | |
Research Site | |
Hangzhou, China, 310016 | |
Research Site | |
Nanjing, China, 210002 | |
Research Site | |
Shanghai, China, 200032 | |
Hong Kong | |
Research Site | |
Hong Kong, Hong Kong | |
Research Site | |
Sha Tin, Hong Kong | |
Italy | |
Research Site | |
Benevento, Italy, 82100 | |
Research Site | |
Milano, Italy, 20133 | |
Research Site | |
Roma, Italy, 00168 | |
Japan | |
Research Site | |
Chuo-ku, Japan, 104-0045 | |
Research Site | |
Kashiwa, Japan, 277-8577 | |
Research Site | |
Osakasayama-shi, Japan, 589-8511 | |
Korea, Republic of | |
Research Site | |
Jung-gu, Korea, Republic of, 41944 | |
Research Site | |
Seo-Gu, Korea, Republic of, 49241 | |
Research Site | |
Seongnam-si, Korea, Republic of, 13620 | |
Research Site | |
Seoul, Korea, Republic of, 03080 | |
Research Site | |
Seoul, Korea, Republic of, 06273 | |
Research Site | |
Seoul, Korea, Republic of, 06351 | |
Research Site | |
Seoul, Korea, Republic of, 138-736 | |
Singapore | |
Research Site | |
Bukit Merah, Singapore, 169610 | |
Research Site | |
Singapore, Singapore, 119228 | |
Research Site | |
Singapore, Singapore, 308433 | |
Spain | |
Research Site | |
Barcelona, Spain, 08035 | |
Research Site | |
Barcelona, Spain, 08036 | |
Research Site | |
Cordoba, Spain, 14004 | |
Research Site | |
Pamplona, Spain, 31008 | |
Taiwan | |
Research Site | |
Kaohsiung City, Taiwan, 83301 | |
Research Site | |
Taipei, Taiwan, 100 | |
Research Site | |
Taoyuan City, Taiwan, 333 |
Study Director: | MedImmune, LLC MedImmune, LLC | MedImmune LLC |
Responsible Party: | MedImmune LLC |
ClinicalTrials.gov Identifier: | NCT02519348 |
Other Study ID Numbers: |
D4190C00022 |
First Posted: | August 10, 2015 Key Record Dates |
Last Update Posted: | December 19, 2020 |
Last Verified: | December 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
Time Frame: | AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure |
Access Criteria: | When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure |
URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Hepatocellular Carcinoma Immunotherapy Antibodies, Monoclonal |
Tremelimumab MEDI4736 Durvalumab |
Carcinoma Carcinoma, Hepatocellular Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Liver Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Liver Diseases Bevacizumab |
Durvalumab Tremelimumab Antibodies, Monoclonal Antineoplastic Agents, Immunological Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Immunologic Factors |