In a phase Ib-II study (MORPHEUS-Liver) reported in The Lancet Oncology, Finn et al found that the addition of tiragolumab, an anti-TIGIT monoclonal antibody, to atezolizumab/bevacizumab improved objective response rate in patients with unresectable, locally advanced, or metastatic hepatocellular carcinoma who had received no prior systemic treatment. TIGIT (T-cell immunoreceptor with Ig and ITIM domains) is an immune checkpoint regulator implicated in unresectable hepatocellular carcinoma and other cancers.
Study Details
In the open-label trial, 58 evaluable patients from sites in China, France, Israel, New Zealand, South Korea, Taiwan, and the United States were randomly assigned 2:1 between August 2020 and February 2022 to receive tiragolumab plus atezolizumab/bevacizumab (n = 40) or atezolizumab/bevacizumab (n = 18) until unacceptable toxicity or loss of clinical benefit. Treatments consisted of tiragolumab at 600 mg, atezolizumab at 1,200 mg, and bevacizumab at 15 mg/kg on day 1 of each 21-day cycle. A total of 40% of patients were Asian and 36% White. The primary outcome measure was objective response rate.
Key Findings
At clinical cutoff (in August 2023), median follow-up was 20.6 months in the tiragolumab group and 14.0 months in the control group. Confirmed objective responses (all partial) were observed in 17 patients (43%, 95% confidence interval [CI] = 27%–59%) in the tiragolumab group vs 2 patients (11%, 95% CI = 1%–35%) in the control group (difference in rate = 31%, 95% CI = 6%–57%). Median response durations were not estimable (95% CI = 13.8 months to not estimable) in tiragolumab group responders vs not estimable (95% CI = not estimable to not estimable) in control group responders. An additional 43% vs 44% of patients had stable disease.
Median progression-free survival was 12.3 months (95% CI = 8.2–17.5 months) in the tiragolumab group vs 4.2 months (95% CI = 1.6–7.4 months) in the control group (hazard ratio [HR] = 0.51, 95% CI = 0.27–0.95); rates at 6 and 12 months were 75% vs 41% and 50% vs 24%.
Safety and Toxicity
Among adverse events of any grade, those more common in the tiragolumab group vs the control group included pruritus (50% vs 17%), arthralgia (33% vs 11%), and diarrhea (30% vs 6%). Grade 3/4 adverse events occurred in 40% vs 50% of patients; the most common were hypertension (15% vs 11%), increased aspartate aminotransferase (8% vs 6%), and proteinuria (5% vs 11%). Serious adverse events occurred in 53% vs 56% of patients. Treatment-related death occurred in one patient in the tiragolumab group (due to cholestasis) and in two patients in the control group (due to esophageal varices hemorrhage and upper gastrointestinal hemorrhage). As stated by the investigators, “The addition of tiragolumab to atezolizumab plus bevacizumab did not appear to result in a substantial worsening of treatment-related or immune-mediated adverse events, and no new safety signals were identified.”
The investigators concluded: “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. Based on these data, further study of combination tiragolumab plus atezolizumab plus bevacizumab is warranted.”
Richard S. Finn, MD, University of California, Los Angeles, is the corresponding author for The Lancet Oncology article.
Disclosures: The study was funded by F. Hoffmann-La Roche and Genentech. For full disclosures of all study authors, visit www.thelancet.com.
