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A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152) (SKYSCRAPER-14)

Primary Purpose

Carcinoma, Hepatocellular

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Atezolizumab
Bevacizumab
Tiragolumab
Placebo
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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 to avoid exposing the embryo. Exclusion Criteria: Pregnancy or breastfeeding 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 Known 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.

Sites / Locations

  • City of Hope Cancer Center; Division of Medical Oncology & Experimental TherapeuticsRecruiting
  • Mercy Medical CenterRecruiting
  • Washington Uni School of MedicineRecruiting
  • Kelsey Seybold ClnicRecruiting
  • Swedish Cancer Institute - Edmonds CampusRecruiting
  • Swedish Cancer Institute - IssaquahRecruiting
  • Swedish Cancer Inst.Recruiting
  • Mengchao Hepatobiliary Hospital Of Fujian Medical UniversityRecruiting
  • Zhejiang Provincial People?s HospitalRecruiting
  • The Second Affiliated Hospital of Anhui Medical UniversityRecruiting
  • Shandong Cancer HospitalRecruiting
  • The First Affiliate Hospital of Guangxi Medical UniversityRecruiting
  • Zhongshan Hospital Fudan UnvierstiyRecruiting
  • Renji Hospital Shanghai Jiaotong University School of MedicineRecruiting
  • Iwate Medical University HospitalRecruiting
  • National Cancer CenterRecruiting
  • CHA Bundang Medical CenterRecruiting
  • Chonnam National University Hwasun HospitalRecruiting
  • Seoul National University HospitalRecruiting
  • Asan Medical CenterRecruiting
  • Samsung Medical CenterRecruiting
  • Ulsan University HosiptalRecruiting
  • Auckland City HospitalRecruiting
  • Wellington HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Atezolizumab + Bevacizumab + Tiragolumab

Atezolizumab + Bevacizumab + Placebo

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Investigator-Assessed Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Overall Survival (OS)

Secondary Outcome Measures

Investigator-Assessed Confirmed Objective Response Rate (ORR) According to RECIST v1.1
Investigator-Assessed Duration of Objective Response (DOR) According to RECIST v1.1
Investigator-Assessed PFS Rate According to RECIST v1.1 at 6 and 12 Months
OS Rate at 1 and 2 Years
Investigator-Assessed PFS According to Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST)
Investigator-Assessed Confirmed ORR According to HCC mRECIST
Investigator-Assessed DOR According to HCC mRECIST
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
The following subscales of the EORTC QLQ-C30 will be used for the assessment: global health status/quality-of-life (GHS/QoL), physical functioning and role functioning. GHS and QoL are scored on a 7-point scale: 1=Very poor to 7=Excellent. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with a higher score indicating a worse outcome. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. A higher score indicates a better outcome.
Change from Baseline in GHS/QoL, Physical Functioning, and Role Functioning Assessed Using the EORTC QLQ-C30
GHS and QoL are scored on a 7-point scale: 1=Very poor to 7=Excellent. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with a higher score indicating a worse outcome. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. A higher score indicates a better outcome.
Percentage of Participants With Adverse Events
Serum Concentrations of Atezolizumab
Serum Concentrations of Tiragolumab
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab

Full Information

First Posted
May 23, 2023
Last Updated
October 5, 2023
Sponsor
Hoffmann-La Roche
Collaborators
Chugai Pharmaceutical
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1. Study Identification

Unique Protocol Identification Number
NCT05904886
Brief Title
A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152)
Acronym
SKYSCRAPER-14
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 14, 2023 (Actual)
Primary Completion Date
September 1, 2026 (Anticipated)
Study Completion Date
September 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
Collaborators
Chugai Pharmaceutical

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
650 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Atezolizumab + Bevacizumab + Tiragolumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Atezolizumab + Bevacizumab + Placebo
Arm Type
Placebo Comparator
Arm Description
Atezolizumab, bevacizumab plus placebo will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Tiragolumab
Other Intervention Name(s)
MTIG7192A
Intervention Description
Tiragolumab will be administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo matching tiragolumab will be administered by IV infusion on Day 1 of each 21-day cycle.
Primary Outcome Measure Information:
Title
Investigator-Assessed Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame
From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
Title
Overall Survival (OS)
Time Frame
From randomization to death from any cause (up to approximately 36 months)
Secondary Outcome Measure Information:
Title
Investigator-Assessed Confirmed Objective Response Rate (ORR) According to RECIST v1.1
Time Frame
From randomization up to approximately 36 months
Title
Investigator-Assessed Duration of Objective Response (DOR) According to RECIST v1.1
Time Frame
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)
Title
Investigator-Assessed PFS Rate According to RECIST v1.1 at 6 and 12 Months
Time Frame
Month 6, Month 12
Title
OS Rate at 1 and 2 Years
Time Frame
Year 1, Year 2
Title
Investigator-Assessed PFS According to Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST)
Time Frame
From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
Title
Investigator-Assessed Confirmed ORR According to HCC mRECIST
Time Frame
From randomization up to approximately 36 months
Title
Investigator-Assessed DOR According to HCC mRECIST
Time Frame
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)
Title
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
Description
The following subscales of the EORTC QLQ-C30 will be used for the assessment: global health status/quality-of-life (GHS/QoL), physical functioning and role functioning. GHS and QoL are scored on a 7-point scale: 1=Very poor to 7=Excellent. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with a higher score indicating a worse outcome. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. A higher score indicates a better outcome.
Time Frame
From randomization up to approximately 36 months
Title
Change from Baseline in GHS/QoL, Physical Functioning, and Role Functioning Assessed Using the EORTC QLQ-C30
Description
GHS and QoL are scored on a 7-point scale: 1=Very poor to 7=Excellent. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with a higher score indicating a worse outcome. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. A higher score indicates a better outcome.
Time Frame
From baseline up to approximately 36 months
Title
Percentage of Participants With Adverse Events
Time Frame
Up to approximately 36 months
Title
Serum Concentrations of Atezolizumab
Time Frame
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)
Title
Serum Concentrations of Tiragolumab
Time Frame
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)
Title
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab
Time Frame
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)
Title
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 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 to avoid exposing the embryo. Exclusion Criteria: Pregnancy or breastfeeding 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 Known 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: CO44668 https://forpatients.roche.com/
Phone
888-662-6728 (U.S. Only)
Email
global-roche-genentech-trials@gene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
Mercy Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202
Country
United States
Individual Site Status
Recruiting
Facility Name
Washington Uni School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Kelsey Seybold Clnic
City
Houston
State/Province
Texas
ZIP/Postal Code
77025
Country
United States
Individual Site Status
Recruiting
Facility Name
Swedish Cancer Institute - Edmonds Campus
City
Edmonds
State/Province
Washington
ZIP/Postal Code
98026
Country
United States
Individual Site Status
Recruiting
Facility Name
Swedish Cancer Institute - Issaquah
City
Issaquah
State/Province
Washington
ZIP/Postal Code
98029
Country
United States
Individual Site Status
Recruiting
Facility Name
Swedish Cancer Inst.
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Individual Site Status
Recruiting
Facility Name
Mengchao Hepatobiliary Hospital Of Fujian Medical University
City
Fuzhou City
ZIP/Postal Code
350025
Country
China
Individual Site Status
Recruiting
Facility Name
Zhejiang Provincial People?s Hospital
City
Hangzhou
ZIP/Postal Code
310014
Country
China
Individual Site Status
Recruiting
Facility Name
The Second Affiliated Hospital of Anhui Medical University
City
Hefei
Country
China
Individual Site Status
Recruiting
Facility Name
Shandong Cancer Hospital
City
Jinan
ZIP/Postal Code
250117
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliate Hospital of Guangxi Medical University
City
Nanning
ZIP/Postal Code
530021
Country
China
Individual Site Status
Recruiting
Facility Name
Zhongshan Hospital Fudan Unvierstiy
City
Shanghai City
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Name
Renji Hospital Shanghai Jiaotong University School of Medicine
City
Shanghai City
ZIP/Postal Code
200127
Country
China
Individual Site Status
Recruiting
Facility Name
Iwate Medical University Hospital
City
Iwate
ZIP/Postal Code
028-3695
Country
Japan
Individual Site Status
Recruiting
Facility Name
National Cancer Center
City
Goyang-si
ZIP/Postal Code
10408
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
CHA Bundang Medical Center
City
Gyeonggi-do
ZIP/Postal Code
13496
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Chonnam National University Hwasun Hospital
City
Jeollanam-do
ZIP/Postal Code
58128
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Ulsan University Hosiptal
City
Ulsan
ZIP/Postal Code
44033
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Auckland City Hospital
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Individual Site Status
Recruiting
Facility Name
Wellington Hospital
City
Wellington
ZIP/Postal Code
6021
Country
New Zealand
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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).

Learn more about this trial

A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152)

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