SCG101 Shows Antiviral and Antitumor Activity in Advanced HBV-Related HCC

SCG101 in advanced HBV-related HCC |

Image Credit: © Sebastian Kaulitzki

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Treatment with SCG101, an autologous hepatitis B virus (HBV)–specific T-cell therapy, led to sustained HBV-DNA and serum hepatitis B surface antigen (HBsAg) clearance in patients with advanced HBV-related hepatocellular carcinoma (HCC), according to findings from a phase 1 trial (NCT06617000) presented at the 2025 European Association for the Study of the Liver Congress.¹

All 17 patients with heavily pretreated HBV-related HCC who received a single infusion of SCG101 in the trial showed rapid declines in serum HBsAg levels. Notably, 94% of patients achieved a reduction in HBsAg levels ranging from 1.0 log₁₀ to 4.6 log₁₀ within 28 days that persisted at levels lower than 100 IU/mL for a maximum of 1 year. Additionally, 23.5% of patients achieved HBsAg loss.

Regarding antitumor activity, 47% of patients had measurable tumor regression following SCG101 infusion. Moreover, at data cutoff, the median overall survival (OS) had not yet been reached.

“The dual antiviral and antitumor effects observed with SCG101 are highly promising, especially in this heavily pre-treated patient population,” Shunda Du, MD, chief of the Liver Surgery Department at the Peking Union Medical College Hospital in Beijing, China, stated in a news release. “The sustained HBsAg clearance and tumor response suggest that SCG101 may offer a novel immunotherapeutic option for patients with HBV-related HCC, addressing an area of significant unmet clinical need.”

Notably, 94% of patients in this trial had received prior nucleoside analogue antiviral therapy, and 72% of patients had liver cirrhosis at baseline. Furthermore, all patients had received 2 or more prior lines of systemic cancer therapy, including immune checkpoint inhibitors.

SCG101 was generally well tolerated and had a good safety profile, according to the news release. Transient alanine transaminase level elevations—which were noted to be consistent with the cytolytic mechanism of SCG101—were reported in 94% of patients but resolved within 14 days. Other common treatment-related adverse effects (AEs) included cytokine release syndrome (CRS), neutropenia, and thrombocytopenia, all of which were deemed manageable and reversible.

“These positive data mark an important step forward in the development of SCG101 and validate our approach of harnessing precision T-cell therapy to target chronic HBV infection and HBV-related liver cancer,” Christy Ma, chief executive officer of SCG Cell Therapy, added in the news release. “SCG101 is the first T-cell receptor [TCR] T-cell therapy to demonstrate both virologic clearance and tumor regression in [patients with] HBV-related HCC. We are encouraged by the data, and we look forward to advancing SCG101 through further clinical development to bring this potentially curative therapy to patients in need.”

SCG101 is an investigational, autologous, TCR T-cell therapy that was designed to selectively target HBV-infected cells by recognizing a specific HBsAg epitope. This therapy triggers both cytolytic and non-cytolytic mechanisms to eliminate HBV-infected hepatocytes, as well as premalignant and HBV-HCC cells.

The phase 1 study is enrolling patients ages 18 to 70 years with histologically or cytologically confirmed, HLA-A *02–expressing HCC who had received prior standard systemic therapies.² Patients need to have Barcelona Clinic Liver Cancer stage B or C disease with a Child-Pugh score of 7 or lower. Other eligibility criteria include serum HBeAg negativity, serum or tumor tissue HBsAg positivity, serum HBV-DNA levels of 1 x 1000 IU/mL or lower, at least 1 measurable lesion at baseline per mRECIST and iRECIST criteria, a life expectancy of at least 3 months, and good organ function.

The study’s end points include the incidence of dose-limiting toxicities and AEs, including serious AEs, CRS, and immune effector cell–associated neurotoxicity syndrome; preliminary clinical efficacy, including overall response rate, disease control rate, duration of response, time to response, progression-free survival, and OS; pharmacodynamics; and the persistence of viral vector copy number.

References

1. SCG Announces Late-Breaking Clinical Data of SCG101 in HBV-Related Hepatocellular Carcinoma Presented at EASL 2025. News release. SCG Cell Therapy Pte Ltd. May 7, 2025. Accessed May 8, 2025. https://www.scgcell.com/newsinfo/8316197.html
2. A study of SCG101 TCR-T cell therpay in the treatment of subjects with hepatitis B virus-related. ClinicalTrials.gov. Updated September 27, 2024. Accessed May 8, 2025. https://clinicaltrials.gov/study/NCT06617000