A randomized, multicenter phase 3 study of durvalumab (D) and tremelimumab (T) as first-line treatment in patients with unresectable hepatocellular carcinoma (HCC): HIMALAYA study
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AbstractBackground: Thus far, sorafenib remains the standard of care for first line systemic therapy in patients with advanced HCC but patient prognosis and quality of life (QOL) continues to be poor. HCC may be responsive to immunotherapy due to higher expression of immunosuppressive cells and upregulation of CTLA-4 and PD-1 immune checkpoints (Gao et al 2009, Hato et al 2014, Pardee & Butterfield 2012). Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are also associated with upregulation of regulatory T cells and PD-L1/PD-1 expression (Miroux et al 2010, Pardee & Butterfield 2012). Blockade of PD-L1/PD-1 or CTLA4 immune checkpoints demonstrated clinical benefit in HCC as monotherapy. In preclinical studies, combination of anti-PD-L1 and anti-CTLA-4 antibodies enhanced anti-tumour activity compared to monotherapy, indicating that the two pathways are non-redundant (Stewart, et al). Early clinical data from a phase I/II trial combining anti-PD-L1 and CTLA-4 (NCT02519348) demonstrated safety and a durable objective response rate (ORR) of 18%, prompting study expansion. Methods: HIMALAYA (NCT03298451) is the first randomized, open-label, multicenter, phase 3 study to assess the efficacy and safety of D+T combination therapy versus sorafenib in the first-line treatment of patients with unresectable, histologically-confirmed HCC. Patients will be randomized to arms evaluating D monotherapy, D+T combination therapy, or sorafenib monotherapy. Patients will be stratified according to macrovascular invasion (yes versus no), etiology of liver disease (HBV versus HCV versus others), and performance status (ECOG 0 vs 1). The primary endpoint for this study is overall survival (OS). Secondary endpoints include ORR, duration of response, disease control rate, progression-free survival, and time to progression according to RECIST v1.1 using investigator assessments. Safety and health-related QoL will also be assessed. Clinical trial information: NCT03298451.
All Author(s) ListAbou-Alfa GK, Chan SL, Furuse J, Galle PR, Kelley RK, Qin SK
Journal nameJournal of Clinical Oncology
Volume Number36
Issue Number15
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesOncology;Oncology

Last updated on 2020-25-10 at 03:26