Immune Checkpoint Therapy vs Target Therapy in Reducing Serum HBsAg Levels in Patients With HBsAg+ Advanced Stage HCC
Status:
Recruiting
Trial end date:
2024-03-31
Target enrollment:
Participant gender:
Summary
It is estimated that over 50% of HCC cases worldwide are related to chronic HBV. There are
approximately 350-400 million people across the world infected with HBV, the majority reside
in or originate from Asia. Each year HBV accounts for 749,000 new cases of HCC and 692,000
HCC-related deaths. The annual incidence of HCC is estimated to be <1% for non-cirrhotic HBV
infected patients and 2-3% for those with cirrhosis.
While the most approved nucleos(t)ide analogues (NA) suppress HBV replication through
inhibition of HBV-DNA polymerase and are reported to reduce the risk of HCC incidence,
however, such risk is not completely eliminated under NA treatment. The recent availability
of commercial quantitative assays of serum hepatitis B surface antigen (HBsAg) has enabled
quantitative HBsAg to be used as a biomarker for prognosis and treatment response in CHB. It
has been suggested that HBsAg decline during lamivudine or entecavir therapy is slower and
less pronounced compared to interferon treatment, despite a higher effect on HBV DNA
suppression. Based on HBsAg kinetics, it has been estimated that the predicted median time to
HBsAg loss in patients treated with lamivudine or entecavir is more than 30 years. Thus,
treatment that can induce rapid decline of HBsAg would have clear advantage in reducing the
treatment duration required to achieve HBsAg-loss.
Interestingly, in a recent preliminary study, 12-weeks of treatment with nivolumab has showed
the modest effect on HBsAg decline in HBeAg negative CHB patients. Thus, in this clinical
trial, the investigator will investigate whether immune checkpoint therapy is more effective
in inducing HBsAg decline compared with target therapy in HBsAg-positive patients with
advanced stage HCC.