Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024;20(28):2049-2057.
doi: 10.1080/14796694.2024.2355863. Epub 2024 Jun 10.

IMbrave152/SKYSCRAPER-14: a Phase III study of atezolizumab, bevacizumab and tiragolumab in advanced hepatocellular carcinoma

Shreya Badhrinarayanan  1 , Christopher Cotter  1 , Huaqi Zhu  1 , Ya-Chen Lin  1 , Masatoshi Kudo  2 , Daneng Li  3
Affiliations

IMbrave152/SKYSCRAPER-14: a Phase III study of atezolizumab, bevacizumab and tiragolumab in advanced hepatocellular carcinoma

Shreya Badhrinarayanan et al. Future Oncol. 2024.

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).

Keywords: Phase III trial; advanced liver cancer; atezolizumab; bevacizumab; hepatocellular carcinoma; overall survival; progression-free survival; safety; tiragolumab; treatment efficacy.

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.

PubMed Disclaimer

Conflict of interest statement

D Li has received honoraria and advisory/consultancy fees from AbbVie, AstraZeneca, Ipsen, Eisai, Exelixis, Coherus, Genentech, QED, Merck, Adagene, Delcath, Servier, Sumitomo, Transthera and TerSera; and received institutional research funding from Brooklyn Immunotherapeutics and AstraZeneca. M Kudo reports the following conflicts of interest: honoraria payment to self from Bayer, Chugai Pharmaceutical Co. Ltd., Eli Lilly, Eisai and Takeda; research funding to institution from AbbVie, Chugai Pharmaceutical Co. Ltd., EA Pharma, Eisai, F. Hoffmann-La Roche Ltd, GE HealthCare, Gilead Sciences, Otsuka, Sumitomo Dainippon Pharma, Taiho and Takeda; and Editor in Chief of Liver Cancer. S Badhrinarayanan, C Cotter, H Zhu and Y-C Lin are employees of Roche/Genentech. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.
Study scheme.
See this image and copyright information in PMC

References

    1. International Agency for Research on Cancer, World Health Organization [Internet]. International Agency for Research on Cancer, Lyon, France. 2024. Available from: https://gco.iarc.fr/today/home
    1. Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019;380(15):1450–1462. doi:10.1056/NEJMra1713263 - DOI - PubMed
    1. Llovet JM, Kelley RK, Villanueva A, et al. . Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6. doi:10.1038/s41572-020-00240-3 - DOI - PubMed
    1. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301–1314. doi:10.1016/S0140-6736(18)30010-2 - DOI - PubMed
    1. Kinoshita A, Onoda H, Fushiya N, et al. . Staging systems for hepatocellular carcinoma: current status and future perspectives. World J Hepatol. 2015;7(3):406–424. doi:10.4254/wjh.v7.i3.406 - DOI - PMC - PubMed

Publication types

MeSH terms

Associated data

Grants and funding