IMbrave152/SKYSCRAPER-14 - a Phase III study - Clinical Trial Protocol

Sep 21, 2026

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A Phase III, randomized, double-blind, placebo-controlled study evaluates IMbrave152/SKYSCRAPER-14 in advanced hepatocellular carcinoma (HCC) without prior systemic treatment. It tests whether adding tiragolumab, targeting TIGIT expressed on immunosuppressive myeloid and T regulatory cells, improves outcomes beyond standard atezolizumab plus bevacizumab. Rationale builds on prior positive efficacy signals from MORPHEUS-Liver. The trial compares tiragolumab versus placebo alongside atezolizumab and bevacizumab, assessing overall survival and progression-free survival, with safety and patient-reported tolerability.

LanguageEnglish

CategoryResearch & Report

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Pages9

Reading Time23 min

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Background & rationale

Hepatocellular carcinoma disease background

CLINICAL TRIAL PROTOCOL IMbrave152/SKYSCRAPER-14: a Phase III study of atezolizumab, bevacizumab and tiragolumab in advanced hepatocellular carcinoma Shreya Badhrinarayanan* , a, Christopher Cottera, Huaqi Zhua, Ya-Chen Lina, Masatoshi Kudob and Daneng Lic a Clinical Development Oncology, Genentech Inc., South San Francisco, CA, USA; b Department of Medicine, Kindai University Faculty of Medicine, Osaka, Japan; c Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA USA ABSTRACT Atezolizumab plus bevacizumab is a standard of care, first-line therapy for advanced hepatocellular carcinoma (HCC) . Myeloid and T regulatory cells are key immunosuppressive cell types within the hepatic tumor microenvironment associated with clinical resistance to atezolizumab and bevacizumab therapy for HCC and overall poor prognosis. Therapeutic targeting of TIGIT, which is highly expressed in these cells, with tiragolumab may overcome the immunosuppressive environment and improve clinical benefit, a hypothesis supported by positive efficacy signals in the Phase Ib/II MORPHEUS-Liver study. This paper describes the rationale and design of IMbrave152/SKYSCRAPER-14, a randomized, double-blind, placebo-controlled Phase III study comparing atezolizumab and bevacizumab with tiragolumab or placebo in patients with HCC and no prior systemic treatment. Clinical Trial Registration: NCT05904886 ([ClinicalTrials.gov](ClinicalTrials.gov)) PLAIN LANGUAGE SUMMARY This research study is designed to test a new treatment combination for liver cancer, specifically for patients whose cancer cannot be removed with surgery or has spread. The treatment involves three medications: atezolizumab, bevacizumab and tiragolumab. Atezolizumab and bevacizumab are already used together as a standard treatment for liver cancer. Tiragolumab is designed to block the TIGIT receptor, which is normally involved in holding back the immune cells that would attack the tumor. Because tiragolumab may restore the immune response against the tumor, adding tiragolumab might make the treatment more effective. The study is being done worldwide and includes patients who have not received any previous systemic treatment for their advanced liver cancer. Patients participating in the study will be randomly placed into two groups. One group will receive the new combination of three medications, while the other group will receive the standard treatment of two medications plus a placebo (a treatment with no active ingredient). The main goal is to see if the new combination helps patients live longer and slows the cancer’s growth compared with the standard treatment. Safety and how patients feel during the treatment are also important parts of the study. TWEETABLE ABSTRACT IMbrave152/SKYSCRAPER-14: New Phase III trial tests atezolizumab, bevacizumab & tiragolumab in advanced HCC, aiming to revolutionize treatment outcomes. \#HCCResearch \#OncologyInnovation ARTICLE HISTORY Received 8 April 2024 Accepted 13 May 2024 KEYWORDS advanced liver cancer; atezolizumab; bevacizumab; hepatocellular carcinoma; overall survival; Phase III trial; progression-free survival; safety; tiragolumab; treatment efficacy 1. Background & rationale 1.1. Hepatocellular carcinoma disease background Primary liver cancer remains a global health challenge. Liver cancer is the third most common cause of cancerrelated death and is the sixth most common in terms of incident cases worldwide [1] . Hepatocellular carcinoma (HCC) accounts for approximately 90% of liver cancer cases [2,3] . The development of HCC is closely related to the presence of chronic liver disease, mostly due to hepatitis B virus or hepatitis C virus, or nonviral causes such as alcohol abuse or nonalcoholic fatty liver disease, resulting in heterogeneous worldwide incidence rates [3] . Most HCC cases (80%) occur in sub-Saharan Africa and eastern Asia, where the mai

FAQs

What is IMbrave152/SKYSCRAPER-14 intended to test?

It tests whether tiragolumab added to atezolizumab plus bevacizumab improves clinical benefit in advanced hepatocellular carcinoma compared with placebo plus standard therapy.

Who can participate in the study?

Patients with advanced HCC who have not received any previous systemic treatment are eligible.

What is the trial’s main goal and what outcomes are assessed?

The main goal is to determine whether the new combination helps patients live longer and slows tumor growth; safety and tolerability are also key aspects.

Sep 21, 2026

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