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

• ClinicalTrials.gov Identifier: NCT05904886
• Recruitment Status: Recruiting
• First Posted: June 15, 2023
• Last Update Posted: April 12, 2024
• Sponsor: Hoffmann-La Roche
• Collaborator: Chugai Pharmaceutical
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: May 23, 2023
• First Posted Date: June 15, 2023
• Last Update Posted Date: April 12, 2024
• Actual Study Start Date: September 14, 2023
• Estimated Primary Completion Date: September 1, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 14, 2023)

• 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) ]
• Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to approximately 36 months) ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 14, 2023)

• Investigator-Assessed Confirmed Objective Response Rate (ORR) According to RECIST v1.1 [ Time Frame: From randomization up to approximately 36 months ]
• 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) ]
• Investigator-Assessed PFS Rate According to RECIST v1.1 at 6 and 12 Months [ Time Frame: Month 6, Month 12 ]
• OS Rate at 1 and 2 Years [ Time Frame: Year 1, Year 2 ]
• 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) ]
• Investigator-Assessed Confirmed ORR According to HCC mRECIST [ Time Frame: From randomization up to approximately 36 months ]
• 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) ]
• 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.
• 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.
• Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 36 months ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152)
• 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
• 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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Carcinoma, Hepatocellular

Intervention

• 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 Name: 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 Name: 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 Name: MTIG7192A
• Other: Placebo
  Placebo matching tiragolumab will be administered by IV infusion on Day 1 of each 21-day cycle.

Study Arms

• 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.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Bevacizumab
  • Drug: Tiragolumab
• 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.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Bevacizumab
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 14, 2023): 650
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 1, 2026
• Estimated Primary Completion Date: September 1, 2026 (Final data collection date for primary outcome measure)

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 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.

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: CO44668 https://forpatients.roche.com/; 888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

• Listed Location Countries: Belgium, Brazil, Côte D'Ivoire, Canada, China, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Mexico, New Zealand, Poland, Puerto Rico, Singapore, South Africa, Spain, Taiwan, Thailand, Turkey, United States

Administrative Information

• NCT Number: NCT05904886
• Other Study ID Numbers: CO44668; 2023-503422-39-00 ( Registry Identifier: EU CT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Chugai Pharmaceutical

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: April 2024