The landscape of hepatocellular carcinoma treatment may be shifting as new data reveals promising results for an innovative immunotherapy combination. In a groundbreaking phase Ib-II MORPHEUS-Liver study, researchers have demonstrated significant improvements in patient outcomes by adding the anti-TIGIT monoclonal antibody tiragolumab to standard first-line treatment for unresectable hepatocellular carcinoma.
The multicenter study, conducted across six countries, showed that patients receiving tiragolumab in combination with atezolizumab (Tecentriq) and bevacizumab (Avastin) achieved a confirmed objective response rate of 43%, nearly four times higher than the 11% observed in patients receiving standard therapy alone.
Survival Advantages and Clinical Impact
The addition of tiragolumab led to substantial improvements in key survival metrics. Median progression-free survival reached 12.3 months in the tiragolumab group, compared to 4.2 months in the control group (HR 0.51, 95% CI 0.27-0.95). Even more striking was the median overall survival benefit, with the tiragolumab combination achieving 28.9 months versus 15.1 months in the control group (HR 0.39, 95% CI 0.19-0.78).
The survival advantage was evident at multiple timepoints, with 6-month progression-free survival rates of 75% versus 41%, and 12-month rates of 50% versus 24% favoring the tiragolumab combination.
Study Design and Patient Population
The trial enrolled 59 patients across 26 centers in China, France, Israel, New Zealand, South Korea, and the United States between August 2020 and February 2022. Eligible participants had previously untreated locally advanced unresectable hepatocellular carcinoma, with an Eastern Cooperative Oncology Group performance status of 0-1. The study population had a median age of 65 years, was predominantly male (79%), and included a diverse ethnic composition with 40% Asian and 36% white participants.
Safety Profile and Adverse Events
While the tiragolumab combination demonstrated enhanced efficacy, it also showed a distinct safety profile. More patients in the tiragolumab group experienced certain adverse events, including:
- Pruritus (50% vs 17%)
- Arthralgia (33% vs 11%)
- Diarrhea (30% vs 6%)
Most adverse events were grade 1-2, with manageable grade 3-4 events including hypertension (15% vs 11%), increased aspartate aminotransferase (8% vs 6%), and proteinuria (5% vs 11%).
Serious adverse events occurred at similar rates between groups (53% tiragolumab vs 56% control), with treatment-related deaths reported in one tiragolumab patient and two control group patients.
Expert Perspectives
Dr. Richard S. Finn of the University of California Los Angeles, the study's lead researcher, emphasized the significance of this being the first randomized, global study to report data for an anti-TIGIT monoclonal antibody in hepatocellular carcinoma.
In an accompanying commentary, Dr. Thomas Yau and colleagues from the University of Hong Kong noted the revolutionary potential of dual immune checkpoint inhibitor regimens while expressing keen interest in the long-term survival implications of the increased response rates observed with tiragolumab.
The researchers acknowledge that while the current standard of atezolizumab plus bevacizumab has improved survival in unresectable hepatocellular carcinoma, the median overall survival remains under two years, highlighting the continued need for more effective first-line treatments. These latest findings suggest that the addition of tiragolumab could represent a promising step forward in addressing this unmet medical need.
