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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05904886




Registration number
NCT05904886
Ethics application status
Date submitted
23/05/2023
Date registered
15/06/2023
Date last updated
10/06/2024

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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Lagos
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Bangkok
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Khon Kaen
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Turkey
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Adana
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Ankara
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Edirne
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Kar?iyaka
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United Kingdom
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Edinburgh
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United Kingdom
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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
The purpose of this study is to assess the efficacy and safety of tiragolumab, an anti-TIGIT
monoclonal antibody, when administered in combination with atezolizumab and bevacizumab as
first-line treatment, in participants with unresectable, locally advanced or metastatic
hepatocellular carcinoma (HCC).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05904886
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05904886