A Study of Durvalumab or Tremelimumab Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Advanced Hepatocellular Carcinoma
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
3 other identifiers
interventional
433
9 countries
44
Brief Summary
This is a multicenter, open-label, stratified, randomized study to evaluate the safety, tolerability, antitumor activity, pharmacokinetics, pharmacodynamics, and immunogenicity of durvalumab or tremelimumab monotherapy, or durvalumab in combination with tremelimumab or bevacizumab in advanced hepatocellular carcinoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 hepatocellular-carcinoma
Started Oct 2015
Longer than P75 for phase_2 hepatocellular-carcinoma
44 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 30, 2015
CompletedFirst Posted
Study publicly available on registry
August 10, 2015
CompletedStudy Start
First participant enrolled
October 19, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 6, 2020
CompletedResults Posted
Study results publicly available
December 6, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 18, 2026
ExpectedJune 3, 2026
May 1, 2026
5.1 years
July 30, 2015
November 5, 2021
May 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was defined as treatment-related toxicity that occurred during DLT evaluation period including: any Grade 4 immune-related adverse event (irAE), any Grade 3 colitis or any Grade 3 noninfectious pneumonitis irrespective of duration, any \>= Grade 2 pneumonitis that does not resolve to \<= Grade 1 within 7 days of initiation of maximal supportive care, any other Grade 3 irAE (excluding colitis or pneumonitis) that does not downgrade to Grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to \<= Grade 1 or baseline within 14 days, liver transaminase elevation \> 8 × upper limit of normal (ULN) or total bilirubin \> 5 × ULN, aspartate aminotransferase or alanine aminotransferase \> 3 × ULN with concurrent increase in total bilirubin \> 2 × ULN without evidence of cholestasis or alternative explanations, and any \>= Grade 3 non-irAE (except for the protocol stated conditions).
From Day 1 to Day 28 after first dose of study drug
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measure at the time of end of study.
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters
Participants with clinically important Common Terminology Criteria for Adverse Events (CTCAE) grade changes to 3 or 4 in hematology and chemistry parameters are reported. There will be no updated results for this outcome measure at the time of end of study.
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Vital sign assessment included pulse rate, blood pressure, temperature, weight, and respiratory rate. Vital signs abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study.
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events
Number of participants with ECG abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study.
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Secondary Outcomes (7)
Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR)
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Disease Control Rate (DCR) Based on Investigator Assessments and BICR
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Time to Response (TTR) Based on Investigator Assessments and BICR
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Duration of Response (DoR) Based on Investigator Assessments and BICR
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Time to Progression (TTP) Based on Investigator Assessments and BICR
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
- +2 more secondary outcomes
Study Arms (9)
Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg
EXPERIMENTALParticipants 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.
Parts 2 and 3: Durvalumab 1500 mg
EXPERIMENTALParticipants 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.
Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg
EXPERIMENTALParticipants 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.
Parts 2 and 3: Tremelimumab 750 mg
EXPERIMENTALParticipants 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.
Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg
EXPERIMENTALParticipants 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.
Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg
EXPERIMENTALParticipants 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
China Cohort: Durvalumab 20 mg/kg
EXPERIMENTALParticipants 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.
China Cohort: Tremelimumab 10 mg/kg
EXPERIMENTALParticipants 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.
China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg
EXPERIMENTALParticipants 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.
Interventions
Tremelimumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
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.
Eligibility Criteria
You may qualify if:
- Male or female participants
- years and older (Japan-20 years and older)
- Confirmed hepatocellular carcinoma (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.
You may not qualify if:
- Prior exposure to immune-mediated therapy
- Hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy
- Gastrointestinal 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MedImmune LLClead
Study Sites (44)
Research Site
Phoenix, Arizona, 85054, United States
Research Site
San Francisco, California, 94158, United States
Research Site
New Haven, Connecticut, 06510, United States
Research Site
Jacksonville, Florida, 32224, United States
Research Site
Tampa, Florida, 33612, United States
Research Site
Indianapolis, Indiana, 46202, United States
Research Site
Boston, Massachusetts, 02114, United States
Research Site
New York, New York, 10065, United States
Research Site
Stony Brook, New York, 11794, United States
Research Site
Durham, North Carolina, 27705, United States
Research Site
Portland, Oregon, 97213, United States
Research Site
Philadelphia, Pennsylvania, 19107, United States
Research Site
Philadelphia, Pennsylvania, 19111, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Dallas, Texas, 75390, United States
Research Site
Seattle, Washington, 98109, United States
Research Site
Hangzhou, 310016, China
Research Site
Nanjing, 210002, China
Research Site
Shanghai, 200032, China
Research Site
Hong Kong, Hong Kong
Research Site
Shatin, Hong Kong
Research Site
Benevento, 82100, Italy
Research Site
Milan, 20133, Italy
Research Site
Roma, 00168, Italy
Research Site
Chūōku, 104-0045, Japan
Research Site
Kashiwa, 277-8577, Japan
Research Site
Osakasayama-shi, 589-8511, Japan
Research Site
Bukit Merah, 169610, Singapore
Research Site
Singapore, 119074, Singapore
Research Site
Singapore, 308433, Singapore
Research Site
Busan, 49241, South Korea
Research Site
Junggu, 41944, South Korea
Research Site
Seongnam-si, 13620, South Korea
Research Site
Seoul, 03080, South Korea
Research Site
Seoul, 05505, South Korea
Research Site
Seoul, 06273, South Korea
Research Site
Seoul, 06351, South Korea
Research Site
Barcelona, 08035, Spain
Research Site
Barcelona, 08036, Spain
Research Site
Córdoba, 14004, Spain
Research Site
Pamplona, 31008, Spain
Research Site
Kaohsiung City, 83301, Taiwan
Research Site
Taipei, 100, Taiwan
Research Site
Taoyuan City, 333, Taiwan
Related Publications (1)
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.
PMID: 34292792DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca Clinical Study Information Center
Study Officials
- STUDY DIRECTOR
MedImmune, LLC MedImmune, LLC
MedImmune LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 30, 2015
First Posted
August 10, 2015
Study Start
October 19, 2015
Primary Completion
November 6, 2020
Study Completion (Estimated)
December 18, 2026
Last Updated
June 3, 2026
Results First Posted
December 6, 2021
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, 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
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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared