691 First-in-human trial of novel HBsAg-specific TCR T cell therapy (SCG101) in patients with HBV-related hepatocellular carcinoma

BackgroundHepatitis B virus (HBV) infection accounts for 75–80% of virus-associated Hepatocellular carcinoma (HCC). HBV DNA integration into the host cell genome produces viral antigens and can lead to tumorigenesis, which can be effectively targeted by HBsAg-specific TCR-T cells. SCG101, a first-in-class autologous HBsAg-specific TCR-T cell therapy, has demonstrated high affinity, avidity, and profound antiviral and antitumor functionalities in preclinical studies. This abstract presents the evaluation of SCG101 in subjects with HBV-related HCC in an investigator-initiated trial.MethodsThe trial enrolled six subjects with advanced HBV-related HCC, HBsAg(+), HBeAg(-), BCLC B/C stage, and HLA-A*02:01 allele, who had received one to three prior systemic therapies and at least 12 months of antiviral treatment (Entecavir and/or Tenofovir). All subjects received a single dose of 5x107 or 1x108 cells/kg SCG101 intravenously after lymphodepletion. Safety, pharmacokinetics (PK), antiviral, and antitumor activities were evaluated.ResultsFollowing infusion, transferred T cells exhibited significant dose-dependent proliferation and demonstrated strong persistence during the study period. SCG101 infusion resulted in a profound antiviral and/or antitumor activities in all six subjects. Serum HBsAg dropped in all six subjects, with four out of six experiencing a reduction of >1 log. Transient ALT elevation correlating with HBsAg reduction was observed in all subjects, indicating the killing of target cells in the liver. Disease control was observed in all subjects (4/4, 100%) with >1 log serum HBsAg reduction, including two partial responses (one cPR and one uPR, according to mRECIST and iRECIST) and two stable diseases (SD). Patients without significant (>1 log) serum HBsAg reduction showed no tumor response. Until data cut-off, the medium progression-free survival (mPFS) was 11 months compared to 0.7 months in subjects with and without >1 log serum HBsAg reduction, respectively. The treatment was well-tolerated, with no dose-limiting toxicity or neurotoxicity reported.ConclusionsSCG101, as a single agent, demonstrated significant antiviral and antitumor activity in subjects with HBV-related HCC. The persistence of TCR+ T cells, reduction of serum HBsAg, and tumor response are strongly correlated with the mechanism of action of SCG101. A phase I/II clinical trial to further evaluate the safety and efficacy of SCG101 is ongoing.Ethics ApprovalThis study was approved by