Early Safety Results from the Phase 3b SIERRA Study of Durvalumab and Tremelimumab as First-Line Treatment for Participants with Unresectable Hepatocellular Carcinoma and a Poor Prognosis

作者：Stephen L. Chan, Masatoshi Kudo, Bruno Sangro, Robin Kate Kelley, Jee Hyun Kim, Binh V. Pham, Jung Yong Hong, Dirk‐Thomas Waldschmidt, Donatella Marino, Joycelyn Jie Xin Lee, René Gerolami, Adam M. Burgoyne, Qiao Li, Hitomi Nakamura, Peng Sun, Boris Baur, Lorenza Rimassa · 发表于：Liver Cancer · 年份：2025 · DOI：10.1159/000549955 · 被引用次数：3 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cancer Immunotherapy and Biomarkers、Bladder and Urothelial Cancer Treatments

Introduction: Subgroups of people with unresectable hepatocellular carcinoma (uHCC) are often excluded from clinical trials due to adverse prognostic factors. The SIERRA (NCT05883644) study assesses the efficacy and safety of STRIDE (Single Tremelimumab Regular Interval Durvalumab) in clinically relevant subgroups of uHCC with poorer prognosis, including participants with more decompensated hepatic function, worse performance status, or more advanced disease than the HIMALAYA (NCT03298451) study. Methods: SIERRA is a phase 3b, single-arm, multicenter study that enrolled participants with uHCC with: Child-Pugh (CP) class of B7 or B8 with Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, without main trunk portal vein thrombosis (PVT) (CP B7/B8 cohort); CP class A with ECOG PS 2, without main trunk PVT (ECOG PS 2 cohort); or CP class A with ECOG PS 0-1 with evidence of chronic main trunk PVT (Vp4 cohort). Participants received STRIDE (tremelimumab 300 mg plus durvalumab 1,500 mg once followed by durvalumab 1,500 mg every 4 weeks). This preplanned early safety analysis occurred once ∼60 participants had been followed for ≥6 months (data cutoff: September 27, 2024). Co-primary endpoints are incidence of grade 3/4 adverse events (AEs) possibly related to study treatment (PRAEs) within 6 months of treatment initiation and objective response rate. The study is ongoing. Results: = 19). Median (Q1-Q3) number of cycles of durvalumab was 4.0 (2.0-8.0). Incidence of gr...