IMbrave150: A randomised phase III study of atezolizumab + bevacizumab vs sorafenib in locally advanced or metastatic hepatocellular carcinoma

Abstract

Background: Advanced hepatocellular carcinoma (HCC) is a disease of high unmet medical need. The multikinase inhibitor sorafenib remains the global 1L standard of care despite considerable toxicities. Single-agent inhibition of PD-L1/PD-1 or VEGF signalling has only modest activity in HCC. However, in a recent Phase Ib study (Lee, ESMO-Asia, 2018, submitted), a response rate of 61% with a manageable safety profile was observed with the combination of atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF). These results are consistent with the hypothesis that bevacizumab, when given with atezolizumab, may further enhance atezolizumab's efficacy by reversing VEGF-mediated immunosuppression and promoting T-cell infiltration into the tumour. Clinical benefit with atezolizumab + bevacizumab has also been observed in Phase III studies of patients with 1L renal cell carcinoma and non-small cell lung cancer. Trial design: IMbrave150 is a global, multicentre, randomised, open-label, Phase III trial enrolling 1L patients (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 or 1. Pts with untreated varices with bleeding or high risk for bleeding or a history of autoimmune disease or immune deficiency will be excluded. Approximately 480 pts will be randomised 2:1 to receive study or standard-of-care control treatment until loss of clinical benefit or unacceptable toxicity (treatments and efficacy endpoints are shown in the table). Stratification factors are ECOG PS (0 vs 1), baseline alpha fetoprotein level (< 400 vs ≥ 400 ng/mL), macrovascular invasion and/or extrahepatic spread (presence vs absence) and region (Asia excluding Japan vs rest of world). (Table Presented).