Phase II multicenter pilot study of safety, efficacy, and immune cell profiling in advanced hepatocellular carcinoma (HCC) on combination of sorafenib (SOR) plus nivolumab (NIVO).
2019
TPS464Background: The antiangiogenic tyrosine kinase inhibitor (TKI) SOR prolongs survival in advanced HCC, but responses occur in fewer than 5% of patients (pts) and median progression-free survival (PFS) is less than 6 months. Immune checkpoint inhibition (CPI) with the PD-1 inhibitor, NIVO, achieved an overall response rate (ORR) of approximately 20% in sorafenib-naive pts enrolled on CheckMate 040 trial though most pts had progression. In preclinical studies, TKI can inhibit regulatory T cells and myeloid derived suppressor cells, immune cell subsets which may contribute to CPI resistance. CD8+ T cells in sorafenib-resistant tumors are characterized by PD-1 expression, providing rationale for a combined approach. The combination of TKI or the anti-angiogenic bevacizumab with CPI improves anti-tumor activity in HCC mouse models and in preliminary clinical studies. This study will examine the safety, maximum tolerated dose (MTD), and ORR of the combination of SOR plus NIVO in advanced HCC pts, along wit...
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