First-in-human Clinical Results of a Novel HBV-specific TCR T Cell Therapy (SCG101) in Patients With HBV-related Hepatocellular Carcinoma (HCC)

SCG101, a first-in-class autologous HBV-specific TCR-T cell therapy that utilizes a natural, high-affinity TCR, has been evaluated for its antiviral and antitumor activities in patients with HBV-related HCC in an investigator-initiated phase I trial.

Six HLA-A*02:01(+), serum HBsAg(+), and HBeAg(-) patients with advanced HBV-related HCC (BCLC B/C), who had received 1-3 prior systemic therapies, were enrolled. All patients received a single dose of SCG101 at 5 x 10E7 or 1 x 10E8 cells/kg intravenously three days after lymphodepletion. Safety, pharmacokinetics, pharmacodynamics, and efficacy of SCG101 were evaluated.

Overall, SCG101 treatment was well-tolerated, with no dose-limiting toxicity or neurotoxicity observed. The most common treatment-related adverse events were elevated liver enzymes, cytokine release syndrome, and cytopenia. After infusion, SCG101 showed dose-dependent proliferation. Serum HBsAg levels dropped in all six patients; four (66.7%) had a reduction>1 log10, with three of them maintaining<10 IU/mL. Transient ALT elevation was observed concurrently in all patients, indicating on-target activity of SCG101. Tumor control was observed in all four patients with HBsAg reduction>1 log10, with two exhibiting a partial response (PR) and two a stable disease (SD) per mRECIST. The median progression-free survival (mPFS) in patients with HBsAg reduction>1 log10 was longer than those without (mPFS: 5.9 vs 0.7 months).

SCG101, as a monotherapy for patients with HBV-related HCC, demonstrated antiviral and antitumor activities alongside a manageable safety profile. The persistence of SCG101, reduction of serum HBsAg, and tumor response collectively underscore its on-target activity.

Publication History

Article published online:
20 January 2025