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

Roche

Status and phase: Enrolling; Phase 3

Conditions: Carcinoma, Hepatocellular

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

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 hepatocellular carcinoma (HCC).

Enrollment: 650 estimated 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
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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650 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: Atezolizumab

Drug: Bevacizumab

Drug: Tiragolumab

Atezolizumab + Bevacizumab + Placebo

Placebo Comparator group

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.

Treatment:

Drug: Atezolizumab

Drug: Bevacizumab

Other: Placebo