Multinational randomized phase 1b-2 study of addition of tiragolumab to atezolizumab-bevacizumab for unresectable, advanced hepatocellular carcinoma

TIGIT is an immune checkpoint regulator implicated in many cancers, including unresectable hepatocellular carcinoma (HCC). The randomized phase 1b-2 MORPHEUS-liver study, at 26 centers in 7 countries, evaluated addition of the anti-TIGIT monoclonal antibody tiragolumab to atezolizumab-bevacizumab for previously untreated, unresectable, locally advanced or metastatic HCC. Patients were randomized 2:1 to tiragolumab-atezolizumab-bevacizumab (TAB; n=40) or atezolizumab-bevacizumab (AB; n=18). Treatment was continued until unacceptable toxic effects or loss of clinical benefit. The primary endpoint was objective response rate. ORR was 43% (95% CI 27-59; n=17) with TAB and 11% (1-35; n=2) with AB. Serious adverse events occurred in 53% with TAB and 56% with AB, and treatment-related deaths in one patient with TAB and two patients with AB. The progression-free survival and overall survival were better in the TAB group than in the AB group. The authors conclude that addition of tiragolumab to atezolizumab-bevacizumab for previously untreated U/M HCC resulted in improved clinical activity.