Background: Advanced HCC is a lethal cancer with a high unmet medical need. Single-agent immunotherapy with PD-L1/PD-1 blockade or treatment (Tx) with anti-angiogenic bevacizumab (bev; anti-VEGF) has shown modest activity in HCC. We hypothesized that the combination of atezolizumab (atezo; anti–PD-L1) + bev results in a greater clinical benefit due to the additional immunomodulatory effects of bev (increased DC maturation, enhanced T-cell infiltration, reduced MDSCs and Tregs in tumors), which create a more favorable tumor microenvironment that potentiates the efficacy of atezo. Methods: Patients (pts) with unresectable or metastatic HCC who were naive to systemic Tx were enrolled in a Phase Ib study cohort (NCT02715531). Pts received atezo (1200 mg) + bev (15 mg/kg) IV every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary objective was to assess the safety and tolerability of the combination. Secondary efficacy endpoints included ORR, PFS, DOR and time to progression (TTP) per RECIST v1.1; and OS. Results: As of the data cutoff (October 24, 2017), 26 pts were evaluable for safety. Tx-related all-grade AEs occurred in 21 pts (81%). Tx-related grade 3-4 AEs were seen in 9 pts (35%), most commonly hypertension (n = 5 [19%]). No grade 5 AEs were observed. Two pts (8%) experienced 3 Tx-related grade 3 serious AEs (autoimmune encephalitis, mental status change and intra-abdominal hemorrhage). Immune-related AEs requiring corticosteroid Tx occurred in 3 pts (12%). Among 21 efficacy-evaluable pts (minimum follow-up, 16 wk; median survival follow-up, 8.3 mo), confirmed partial responses occurred in 13 pts (62%) regardless of HCC etiology, region (Asia or US), baseline a-fetoprotein levels (≥ or < 400 ng/mL) or extrahepatic spread of tumor. The median estimates for PFS, DOR, TTP and OS have not yet been reached. Conclusions: The combination of atezo + bev is safe and well tolerated; no new safety signals were identified beyond the established safety profile for each agent. The confirmed response rate of 62% suggests that atezo + bev in combination has synergistic clinical activity. Expansion of this HCC cohort and evaluation of atezo + bev in a Phase III study are under way. Clinical trial information: NCT02715531