Addition of Tiragolumab Shows Promise for Locally Advanced, Unresectable Hepatocellular Carcinoma

According to results from the phase 1b/2 MORPHEUS-Liver trial, the addition of tiragolumab to atezolizumab plus bevacizumab demonstrated promise among patients with previously untreated locally advanced or unresectable hepatocellular carcinoma. 

“Although atezolizumab plus bevacizumab was the first treatment regimen to show improved survival versus sorafenib, novel and more efficacious treatment combinations are still needed,” stated Richard Finn, MD, University of California, Los Angeles, California, and coauthors. “Tiragolumab is a human anti-TIGIT monoclonal antibody, which might synergise with other immunotherapies, such as atezolizumab, to improve activation and effectiveness of T-cell and natural killer cell activity and enhance antitumour response.” 

In this study, 58 patients with previously untreated locally advanced or unresectable hepatocellular carcinoma were randomized on a 2-to-1 basis to receive 1200 mg of atezolizumab plus 15 mg/kg of bevacizumab alone (n = 17) or with 600 mg of tiragolumab (n = 41) once every 3 weeks on day 1 of each 21-day cycle until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). A key secondary end point was safety. 

At analysis, the confirmed ORR was 43% in the tiragolumab arm and 11% in the control arm. The most common grade 3/4 adverse events included hypertension, aspartate aminotransferase increase, and proteinuria. Serious adverse events occurred in 53% of patients in the tiragolumab arm and 56% of patients in the control arm. One treatment-related death was reported in the tiragolumab arm and 2 were reported in the control arm.

“This signal-seeking study suggests that the addition of tiragolumab to atezolizumab and bevacizumab might be more clinically active than atezolizumab plus bevacizumab alone in unresectable hepatocellular carcinoma,” concluded Dr Finn et al. “Based on these data, further study of combination tiragolumab plus atezolizumab plus bevacizumab is warranted.”

Source: 

Finn RS, Ryoo BY, Hsu CH, et al. Tiragolumab in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (MORPHEUS-Liver): A randomised, open-label, phase 1b–2, study. Lancet Oncol. Published online: January 21, 2025. doi: 10.1016/S1470-2045(24)00679-X