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

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 invasion and/or extrahepatic spread (presence vs absence), baseline α-fetoprotein level ( < 400 vs ≥ 400 ng/mL) and ECOG PS (0 vs 1). Pts will be randomized 2:1 to receive atezo (1200 mg) plus bev (15 mg/kg) IV Q3W or sor (400 mg) PO BID until loss of clinical benefit or unacceptable toxicity. No crossover will be allowed. Co-primary and secondary efficacy endpoints are listed in Table. ≈ 480 pts are planned to be enrolled globally. Clinical trial information: NCT03434379.Efficacy endpoints. Co-primary ORR (investigator [INV]-assessed per RECIST v1.1), OS Secondary PFS, DOR, TTP (INV-assessed per RECIST v1.1) ORR, PFS, DOR, TTP (independent review facility (IRF)-assessed per RECIST v1.1) ORR, PFS, DOR, TTP (IRF-assessed per HCC mRECIST)