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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05904886




Registration number
NCT05904886
Ethics application status
Date submitted
23/05/2023
Date registered
15/06/2023

Titles & IDs
Public title
A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152)
Scientific title
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
Secondary ID [1] 0 0
2023-503422-39-00
Secondary ID [2] 0 0
CO44668
Universal Trial Number (UTN)
Trial acronym
SKYSCRAPER-14
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Hepatocellular 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Tiragolumab
Other interventions - Placebo

Experimental: Atezolizumab + Bevacizumab + Tiragolumab - Atezolizumab plus bevacizumab plus tiragolumab will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Placebo comparator: Atezolizumab + Bevacizumab + Placebo - Atezolizumab, bevacizumab plus placebo will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator.


Treatment: Drugs: Atezolizumab
Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.

Treatment: Drugs: Bevacizumab
Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.

Treatment: Drugs: Tiragolumab
Tiragolumab will be administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle.

Other interventions: Placebo
Placebo matching tiragolumab will be administered by IV infusion on Day 1 of each 21-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Investigator-Assessed Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Timepoint [1] 0 0
From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
From randomization to death from any cause (up to approximately 36 months)
Secondary outcome [1] 0 0
Investigator-Assessed Confirmed Objective Response Rate (ORR) According to RECIST v1.1
Timepoint [1] 0 0
From randomization up to approximately 36 months
Secondary outcome [2] 0 0
Investigator-Assessed Duration of Objective Response (DOR) According to RECIST v1.1
Timepoint [2] 0 0
From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
Secondary outcome [3] 0 0
Investigator-Assessed PFS Rate According to RECIST v1.1 at 6 and 12 Months
Timepoint [3] 0 0
Month 6, Month 12
Secondary outcome [4] 0 0
OS Rate at 1 and 2 Years
Timepoint [4] 0 0
Year 1, Year 2
Secondary outcome [5] 0 0
Investigator-Assessed PFS According to Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST)
Timepoint [5] 0 0
From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
Secondary outcome [6] 0 0
Investigator-Assessed Confirmed ORR According to HCC mRECIST
Timepoint [6] 0 0
From randomization up to approximately 36 months
Secondary outcome [7] 0 0
Investigator-Assessed DOR According to HCC mRECIST
Timepoint [7] 0 0
From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
Secondary outcome [8] 0 0
Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer 30 (QLQ-C30) Subscales
Timepoint [8] 0 0
From randomization up to approximately 36 months
Secondary outcome [9] 0 0
Change from Baseline in GHS/QoL, Physical Functioning, and Role Functioning Assessed Using the EORTC QLQ-C30
Timepoint [9] 0 0
From baseline up to approximately 36 months
Secondary outcome [10] 0 0
Percentage of Participants With Adverse Events
Timepoint [10] 0 0
Up to approximately 36 months
Secondary outcome [11] 0 0
Serum Concentrations of Atezolizumab
Timepoint [11] 0 0
Prior to the first infusion and 30 minutes after atezolizumab infusion on Day 1 of Cycle 1 (cycle = 21 days), prior to infusion on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit (up to approximately 36 months)
Secondary outcome [12] 0 0
Serum Concentrations of Tiragolumab
Timepoint [12] 0 0
Prior to the first infusion and 30 minutes after tiragolumab infusion on Day 1 of Cycle 1 (cycle = 21 days), prior to infusion on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit (up to approximately 36 months)
Secondary outcome [13] 0 0
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab
Timepoint [13] 0 0
Prior to the first infusion on Day 1 of Cycles (cycle = 21 days) 1, 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit (up to approximately 36 months)
Secondary outcome [14] 0 0
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Timepoint [14] 0 0
Prior to the first infusion on Day 1 of Cycles (cycle = 21 days) 1, 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit (up to approximately 36 months)

Eligibility
Key inclusion criteria
* Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants
* Disease that is not amenable to curative surgical and/or locoregional therapies
* No prior systemic treatment for locally advanced or metastatic and/or unresectable HCC
* Measurable disease according to RECIST v1.1
* ECOG Performance Status of 0 or 1 within 7 days prior to randomization
* Child-Pugh Class A within 7 days prior to randomization
* Adequate hematologic and end-organ function
* Female participants of childbearing potential must be willing to avoid pregnancy within 5 months after the final dose of atezolizumab, within 6 months after the final dose of bevacizumab, and within 90 days after the final dose of tiragolumab/placebo
* Male participants with a female partner of childbearing potential or pregnant female partner must remain abstinent or use a condom during the treatment period and for 6 months after the final dose of bevacizumab and for 90 days after the final dose of tiragolumab/placebo to avoid exposing the embryo.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnancy or breastfeeding within 5 months after the final dose of atezolizumab, within 6 months after the final dose of bevacizumab, and within 90 days after the final dose of tiragolumab/placebo
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Treatment with locoregional therapy to liver within 28 days prior to initiation of study treatment, or non-recovery from side effects of any such procedure
* Treatment with systemic immunostimulatory agents
* Treatment with systemic immunosuppressive medication
* Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding
* A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
* Active or history of autoimmune disease or immune deficiency
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
* Mixed histology or other subtypes/variants of HCC, including, but not limited to, known liver adenocarcinoma, fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC
* Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV)
* Acute Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/09/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2026
Actual
Sample size
Target
650
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
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Xi'an
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Wellington
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JOS
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Lagos
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Poland
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Gdansk
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Singapore
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Polokwane
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Pretoria
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Asturias
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Navarra
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Burgos
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Jaen
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Madrid
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Valencia
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Thailand
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Bangkok
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Thailand
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ChiangMai
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Thailand
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Khon Kaen
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Diyarbakir
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Turkey
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Edirne
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Turkey
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Kar?iyaka
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United Kingdom
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Edinburgh
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United Kingdom
State/province [152] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Chugai Pharmaceutical
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: CO44668 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. Only)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05904886