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

Roche

Status and phase: Active, not recruiting; Phase 3

Conditions: Hepatocellular Carcinoma

Treatments: Other: Placebo; Drug: Bevacizumab; Drug: Atezolizumab; Drug: Tiragolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05904886

2023-503422-39-00 (Registry Identifier)

CO44668

Details and patient eligibility

About

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 HCC.

Per amendment version 5, following a memo issued by the Sponsor, participants receiving treatment in the atezolizumab plus bevacizumab plus tiragolumab arm are recommended to discontinue tiragolumab treatment unless the investigator decides the benefit outweighs the risk. Participants receiving treatment in atezolizumab plus bevacizumab plus placebo arm must discontinue placebo treatment. Participants may continue receiving active treatment(s) per protocol until loss of clinical benefit or unacceptable toxicity, whichever occurs first.

Enrollment: 687 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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
• Eastern cooperative oncology group (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 cluster of differentiation 137 (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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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687 participants in 2 patient groups, including a placebo group

Atezolizumab + Bevacizumab + Tiragolumab

Experimental group

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.

Treatment:

Drug: Tiragolumab

Drug: Bevacizumab

Drug: Atezolizumab

Atezolizumab + Bevacizumab + Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Bevacizumab

Drug: Atezolizumab

Other: Placebo