IMbrave150: A randomized phase III study of 1L atezolizumab plus bevacizumab vs sorafenib in locally advanced or metastatic hepatocellular carcinoma.

作者：Richard S. Finn, Michel Ducreux, Shukui Qin, Peter R. Galle, Andrew X. Zhu, Masafumi Ikeda, Tae‐You Kim, Derek-Zhen Xu, Wendy Verret, Juan Liu, William Grossman, Ann‐Lii Cheng · 发表于：Journal of Clinical Oncology · 年份：2018 · DOI：10.1200/jco.2018.36.15_suppl.tps4141 · 被引用次数：57 · 研究领域：Ferroptosis and cancer prognosis、Hepatocellular Carcinoma Treatment and Prognosis、Bladder and Urothelial Cancer Treatments

TPS4141 Background: Hepatocellular carcinoma (HCC) is a lethal disease with the highest mortality-to-incidence ratio of any solid tumor. The current standard of care for 1L treatment of patients (pts) with locally advanced or metastatic HCC is sorafenib (sor), a multikinase inhibitor. Single-agent treatment involving inhibition of PD-L1/PD-1 immune checkpoint or VEGF has shown modest activity in HCC. Evidence from a Phase I study (Stein ASCO 2018, submitted) in HCC supports a strong scientific rationale for combining atezolizumab (atezo; anti–PD-L1) with bevacizumab (bev; anti-VEGF) to achieve greater clinical benefit. In addition to its anti-angiogenic activity, bev may have immunomodulatory effects in the tumor microenvironment (increased DC maturation, enhanced T-cell infiltration, reduced MDSCs and Tregs in tumors) that can potentially increase the efficacy of atezo in inhibiting PD-L1/PD-1 signaling and restoring anti-tumor T-cell activity. Methods: IMbrave150 (YO40245) is a Phase III, open-label, multicenter, randomized study to evaluate atezo + bev vs sor in pts with locally advanced or metastatic and/or unresectable HCC. Eligible pts will be naive to prior systemic therapy for HCC, have ≥ 1 measurable untreated lesion (per RECIST v1.1), Child-Pugh class A liver function and ECOG PS 0/1. Pts with bleeding or high risk for bleeding with untreated varices will be excluded. Randomization will be stratified by region (Asia [excluding Japan] vs rest of world), macrovascular...