A Study of Durvalumab or Tremelimumab Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Advanced Hepatocellular Carcinoma
NCT ID: NCT02519348
Last Updated: 2025-10-14
Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE2
433 participants
INTERVENTIONAL
2015-10-19
2026-04-01
Brief Summary
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Detailed Description
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* In Part 1 (both 1A and 1B), participants will receive tremelimumab 1 mg/kg intravenous (IV) every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W.
* In Part 2A, participants will be randomized in a 1:1:1 ratio to receive:
* Durvalumab 20 mg/kg Q4W
* Tremelimumab 10 mg/kg Q4W × 7 doses followed by every 12 weeks (Q12W)
* Tremelimumab 1 mg/kg Q4W × 4 doses + durvalumab 20 mg/kg Q4W, followed by durvalumab 20 mg/kg Q4W
* In China cohort, Part 2A study design will be followed.
* In Part 2B, participants will receive tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W.
* In Part 3, participants will be randomized in a 2:2:1:2 ratio to receive:
* Durvalumab 1500 mg Q4W
* Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W
* Tremelimumab 750 mg Q4W for 7 doses followed by Q12W
* Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W, followed by durvalumab 1500 mg Q4W.
Following protocol amendment 5, enrollment into 'Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg' arm will close. Participants will be randomized at a ratio of 2:1:2 in 'Durvalumab 1500 mg Q4W', 'Tremelimumab 750 mg Q4W for 7 doses followed by Q12W', and 'Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W' arms, respectively.
• In Part 4, participants will receive durvalumab 1120 mg (15 mg/kg) + bevacizumab 15 mg/kg every 3 weeks (Q3W).
Participants will receive the treatment until confirm progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
All participants will be followed for survival until the end of study visit (last participant discontinues the study treatment).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg
Participants in Part 1A (safety run-in cohort) and Part 1 B (efficacy-gating cohort) will receive tremelimumab 1 mg/kg every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
Tremelimumab
Tremelimumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Durvalumab
Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Parts 2 and 3: Durvalumab 1500 mg
Participants will receive durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
Durvalumab
Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg
Participants will receive tremelimumab 300 mg 1 dose and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow, or development of other reason for treatment discontinuation, whichever occurs first.
Tremelimumab
Tremelimumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Durvalumab
Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Parts 2 and 3: Tremelimumab 750 mg
Participants will receive tremelimumab 750 mg Q4W 7 doses followed by every 12 weeks (Q12W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
Tremelimumab
Tremelimumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg
Participants will receive tremelimumab 75 mg Q4W 4 doses and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. Participant recruitment to this arm was closed following protocol amendment 5.
Tremelimumab
Tremelimumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Durvalumab
Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg
Participants will receive durvalumab 1120 mg and bevacizumab 15 mg/kg every 3 weeks (Q3W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first
Durvalumab
Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Bevacizumab
Bevacizumab 15 mg/kg will be administered by IV infusion every 3 weeks until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first.
China Cohort: Durvalumab 20 mg/kg
Participants will receive durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
Durvalumab
Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
China Cohort: Tremelimumab 10 mg/kg
Participants will receive tremelimumab 10 mg/kg Q4W 7 doses followed by Q12W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
Tremelimumab
Tremelimumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg
Participants will receive tremelimumab 1 mg/kg Q4W 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
Tremelimumab
Tremelimumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Durvalumab
Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Interventions
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Tremelimumab
Tremelimumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Durvalumab
Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Bevacizumab
Bevacizumab 15 mg/kg will be administered by IV infusion every 3 weeks until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. 18 years and older (Japan-20 years and older)
3. Confirmed hepatocellular carcinoma (HCC) based on histopathological findings from tumor tissues. Advanced HCC with diagnosis confirmed pathologically or with noninvasive methods.
4. Immunotherapy-naïve
5. 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
2. Hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy
3. Gastrointestinal bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
4. Ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose.
5. Main portal vein thrombosis (Vp4) as documented on imaging
6. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment
7. Active or prior documented autoimmune or inflammatory disease with some exceptions
8. Current or prior use of immunosuppressive medication within 14 days with some exceptions
18 Years
99 Years
ALL
No
Sponsors
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MedImmune LLC
INDUSTRY
Responsible Party
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Principal Investigators
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MedImmune, LLC MedImmune, LLC
Role: STUDY_DIRECTOR
MedImmune LLC
Locations
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Research Site
Phoenix, Arizona, United States
Research Site
San Francisco, California, United States
Research Site
New Haven, Connecticut, United States
Research Site
Jacksonville, Florida, United States
Research Site
Tampa, Florida, United States
Research Site
Indianapolis, Indiana, United States
Research Site
Boston, Massachusetts, United States
Research Site
New York, New York, United States
Research Site
Stony Brook, New York, United States
Research Site
Durham, North Carolina, United States
Research Site
Portland, Oregon, United States
Research Site
Philadelphia, Pennsylvania, United States
Research Site
Philadelphia, Pennsylvania, United States
Research Site
Nashville, Tennessee, United States
Research Site
Dallas, Texas, United States
Research Site
Seattle, Washington, United States
Research Site
Hangzhou, , China
Research Site
Nanjing, , China
Research Site
Shanghai, , China
Research Site
Hong Kong, , Hong Kong
Research Site
Shatin, , Hong Kong
Research Site
Benevento, , Italy
Research Site
Milan, , Italy
Research Site
Roma, , Italy
Research Site
Chūōku, , Japan
Research Site
Kashiwa, , Japan
Research Site
Osakasayama-shi, , Japan
Research Site
Bukit Merah, , Singapore
Research Site
Singapore, , Singapore
Research Site
Singapore, , Singapore
Research Site
Busan, , South Korea
Research Site
Junggu, , South Korea
Research Site
Seongnam-si, , South Korea
Research Site
Seoul, , South Korea
Research Site
Seoul, , South Korea
Research Site
Seoul, , South Korea
Research Site
Seoul, , South Korea
Research Site
Barcelona, , Spain
Research Site
Barcelona, , Spain
Research Site
Córdoba, , Spain
Research Site
Pamplona, , Spain
Research Site
Kaohsiung City, , Taiwan
Research Site
Taipei, , Taiwan
Research Site
Taoyuan, , Taiwan
Countries
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References
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Kelley RK, Sangro B, Harris W, Ikeda M, Okusaka T, Kang YK, Qin S, Tai DW, Lim HY, Yau T, Yong WP, Cheng AL, Gasbarrini A, Damian S, Bruix J, Borad M, Bendell J, Kim TY, Standifer N, He P, Makowsky M, Negro A, Kudo M, Abou-Alfa GK. Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. J Clin Oncol. 2021 Sep 20;39(27):2991-3001. doi: 10.1200/JCO.20.03555. Epub 2021 Jul 22.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Other Identifiers
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2024-517085-41-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
2015-001663-39
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
D4190C00022
Identifier Type: -
Identifier Source: org_study_id
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