Clinical results of an HBV-specific T-cell receptor-T-cell therapy (SCG101) in patients with HBV-related hepatocellular carcinoma treated in an investigator-initiated, interventional trial.

Background: SCG101 is an autologous T-cell therapy specifically targeting hepatitis B virus (HBV) using a natural, high-affinity T-cell receptor that is stably expressed.

Objective: We evaluated the safety, pharmacokinetics, pharmacodynamics and efficacy of SCG101 in patients with HBV-related hepatocellular carcinoma (HCC) in an investigator-initiated trial.

Design: Six human leucocyte antigen (HLA)-A*02:01-positive, serum hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen-negative patients with advanced HBV-HCC, who had failed one to three prior systemic therapies, received SCG101 at doses of 5×10 or 1×10 TCR-T cells/kg three days after lymphodepletion.

Results: Within 1 week, all patients experienced a significant but transient alanine aminotransferase elevation paralleled by a 76±57 fold expansion of T cells detected in peripheral blood. No neurotoxicity, but a cytokine release syndrome reaching up to grade 3 was observed. However, these side effects were not dose-limiting and could be managed with corticosteroids, anti-interleukin-6 and/or vasopressor therapy. Indicating on-target activity of SCG101, serum HBsAg levels dropped by 1.96 (0.16-3.84) log within 2 weeks. According to modified Response Evaluation Criteria in Solid Tumours, three of the six patients achieved tumour shrinkage with a best percentage change in target lesion size of -19.5%, -74.6% and -100%. One showed complete remission of the target lesion, remaining progression-free for 27 months and one other achieved a durable (>6 months) remission. During follow-up (median 10.9 months), three patients died, and one was lost to follow-up.

Conclusion: As monotherapy for patients with HBV-HCC, SCG101 demonstrated pronounced antiviral and antitumour activities and a safety profile manageable with supportive care. SCG101's T-cell expansion, serum HBsAg drop and tumour response collectively underscore on-target activity.

Trial Registration Number: NCT05339321.