Early sofosbuvir-based DAAs + atezolizumab/bevacizumab boosts circulating T-cells but yields 0% ORR in HCV-HCC

In the open-label, single-arm Phase IV NCT05717400 trial, patients with HCV-associated advanced HCC received first-line atezolizumab (PD-L1) plus bevacizumab (VEGF) alongside early direct-acting antivirals (sofosbuvir/velpatasvir or sofosbuvir/velpatasvir/voxilaprevir) started within weeks of immunotherapy (n=2 enrolled/treated). Best overall response was stable disease in both patients (ORR 0%; DCR 100%) with sustained virologic response and no Grade 3/4 adverse events; by contrast, the IMbrave150 benchmark for atezo/bev in unresectable HCC reported ORR ~28% per RECIST 1.1 and median PFS ~6.8–6.9 months (vs ~11% ORR and ~4.3 months with sorafenib), so these 2 cases look below expected antitumor activity (though n is far too small to interpret efficacy). Immune correlates suggested increased peripheral CD4+ and CD8+ T-cell frequencies over time and post-DAA tumor immune-cell changes (increased T-cell density in one case; cytotoxic T-cell/macrophage infiltration in the other), but without clear shifts in common activation markers.