History of Changes for Study: NCT05904886

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

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Study Record Versions

Version	Submitted Date	Changes
1	June 14, 2023	None (earliest Version on record)
2	July 13, 2023	Study Status
3	August 10, 2023	Recruitment Status, Study Status and Contacts/Locations
4	September 11, 2023	Study Status and Contacts/Locations
5	October 5, 2023	Study Status and Contacts/Locations
6	November 2, 2023	Contacts/Locations and Study Status
7	November 16, 2023	Contacts/Locations, Eligibility, Study Status and Study Identification
8	November 30, 2023	Contacts/Locations and Study Status
9	December 21, 2023	Contacts/Locations and Study Status
10	January 18, 2024	Contacts/Locations and Study Status
11	February 15, 2024	Contacts/Locations and Study Status
12	March 13, 2024	Contacts/Locations and Study Status
13	April 11, 2024	Contacts/Locations and Study Status
14	May 10, 2024	Contacts/Locations and Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	CO44668
Brief Title:	A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152) (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
Secondary IDs:	2023-503422-39-00 [Registry Identifier: EU Trial Number]

Study Status


Record Verification:	June 2023
Overall Status:	Not yet recruiting
Study Start:	July 31, 2023
Primary Completion:	September 1, 2026 [Anticipated]
Study Completion:	September 1, 2026 [Anticipated]

First Submitted:	May 23, 2023
First Submitted that Met QC Criteria:	June 14, 2023
First Posted:	June 15, 2023 [Actual]

Last Update Submitted that Met QC Criteria:	June 14, 2023
Last Update Posted:	June 15, 2023 [Actual]

Sponsor/Collaborators


Sponsor:	Hoffmann-La Roche
Responsible Party:	Sponsor
Collaborators:	Chugai Pharmaceutical

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

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).
Detailed Description:

Conditions


Conditions:	Carcinoma, Hepatocellular
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	650 [Anticipated]

Arms and Interventions

Arms

Assigned Interventions

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.

Drug: Atezolizumab

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

Other Names:

Tecentriq

Drug: Bevacizumab

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

Other Names:

Avastin

Drug: Tiragolumab

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

Other Names:

MTIG7192A

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.

Drug: Atezolizumab

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

Other Names:

Tecentriq

Drug: Bevacizumab

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

Other Names:

Avastin

Placebo

Placebo matching tiragolumab will be administered by IV infusion on Day 1 of each 21-day cycle.

Outcome Measures


Primary Outcome Measures:
1.	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) ]
2.	Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to approximately 36 months) ]
Secondary Outcome Measures:
1.	Investigator-Assessed Confirmed Objective Response Rate (ORR) According to RECIST v1.1 [ Time Frame: From randomization up to approximately 36 months ]
2.	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) ]
3.	Investigator-Assessed PFS Rate According to RECIST v1.1 at 6 and 12 Months [ Time Frame: Month 6, Month 12 ]
4.	OS Rate at 1 and 2 Years [ Time Frame: Year 1, Year 2 ]
5.	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) ]
6.	Investigator-Assessed Confirmed ORR According to HCC mRECIST [ Time Frame: From randomization up to approximately 36 months ]
7.	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) ]
8.	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 [ Time Frame: From randomization up to approximately 36 months ] 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.
9.	Change from Baseline in GHS/QoL, Physical Functioning, and Role Functioning Assessed Using the EORTC QLQ-C30 [ Time Frame: From baseline up to approximately 36 months ] 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.
10.	Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 36 months ]
11.	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) ]
12.	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) ]
13.	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) ]
14.	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) ]

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
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.

Contacts/Locations


Central Contact Person:	Reference Study ID Number: CO44668 https://forpatients.roche.com/ Telephone: 888-662-6728 (U.S. Only) Email: global-roche-genentech-trials@gene.com
Study Officials:	Clinical Trials Study Director Hoffmann-La Roche
Locations:

IPDSharing


Plan to Share IPD:	Yes 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).
	Supporting Information:
	Time Frame:
	Access Criteria:
	URL:

References


Citations:
Links:
Available IPD/Information: