SCG Cell Therapy has presented groundbreaking clinical data from its Phase 1 trial of SCG101, showing both strong antiviral and antitumor effects in patients with advanced hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The late-breaking results were unveiled at the European Association for the Study of the Liver (EASL) Congress 2025.
The trial evaluated SCG101, an autologous HBV-specific T cell receptor (TCR)-T cell therapy, in a heavily pre-treated patient population with HBV-related liver cancer. Following a single infusion, the therapy demonstrated remarkable efficacy in clearing viral markers while simultaneously showing promising antitumor activity.
Dual Mechanism Shows Promising Results
In this groundbreaking study, 17 patients with advanced HBV-related HCC received SCG101 treatment. The patient population was particularly challenging, with 94% having previously received nucleoside analogue antiviral therapy and 72% presenting with liver cirrhosis at baseline.
The results were striking: all treated patients experienced a rapid decline in serum hepatitis B surface antigen (HBsAg), with 94% (16/17) achieving a 1.0–4.6 log₁₀ reduction within 28 days. This reduction persisted below 100 IU/mL for up to one year. Most notably, 4 patients (23.5%) achieved complete HBsAg loss.
"The dual antiviral and antitumor effects observed with SCG101 are highly promising, especially in this heavily pre-treated patient population," said Prof. Dr. Shunda Du, Chief of Liver Surgery Department at Peking Union Medical College Hospital. "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."
Antitumor Activity in Treatment-Resistant Patients
Beyond its antiviral effects, SCG101 demonstrated encouraging antitumor activity. Despite all patients having received at least two prior lines of systemic cancer treatment, including immune checkpoint inhibitors, 8 out of 17 patients (47%) showed measurable tumor regression. At the time of data cutoff, the median overall survival had not yet been reached, suggesting potential durability of response.
This dual effect addresses a critical need in HBV-related HCC treatment, where both the viral infection and the cancer must be targeted simultaneously for optimal outcomes.
Manageable Safety Profile
SCG101 was generally well tolerated, with a favorable safety profile. Transient alanine aminotransferase (ALT) elevation, consistent with the therapy's cytolytic mechanism, was observed in 94% of patients but resolved within 14 days. Other common treatment-related adverse events included cytokine release syndrome (CRS), neutropenia, and thrombocytopenia—all of which were manageable and reversible.
Mechanism of Action
SCG101 is designed to selectively target and eliminate HBV-infected hepatocytes and HCC cells by recognizing specific epitopes of HBV surface antigen presented via the major histocompatibility complex. The therapy triggers both cytolytic and non-cytolytic mechanisms to effectively eliminate HBV-infected hepatocytes as well as premalignant and HBV-HCC cells with HBV-DNA integration.
The technology is powered by SCG's proprietary GianT™ TCR screening platform, which enables the discovery of natural, high-affinity, high-avidity TCRs against intracellular antigens.
Addressing a Major Global Health Burden
HBV remains a significant global health challenge, affecting over 250 million people worldwide. It is a leading cause of liver cancer, responsible for 50%–80% of hepatocellular carcinoma cases globally. Chronic HBV infection leads to the integration of HBV DNA into the host genome, resulting in persistent HBsAg expression, chromosomal instability, and activation of oncogenes, thereby contributing to the development of hepatocellular carcinoma.
Hepatocellular carcinoma is the most common type of liver cancer. In 2020, it was estimated that over 905,000 new cases of liver cancer were diagnosed, and more than 830,100 deaths occurred globally, making it one of the leading causes of cancer-related mortality. HCC is typically diagnosed at an advanced stage, contributing to a poor prognosis with a five-year survival rate of less than 15%.
Future Directions
"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," said Christy Ma, Chief Executive Officer of SCG Cell Therapy. "SCG101 is the first TCR-T cell therapy to demonstrate both virologic clearance and tumor regression in HBV-related HCC patients. 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."
SCG Cell Therapy, headquartered in Singapore with operations across Singapore, China, and Germany, is focused on developing novel immunotherapies for infectious diseases and associated cancers. The company is advancing a broad pipeline of TCR-based therapeutics aimed at preventing and curing infection-related cancers, including those caused by Helicobacter pylori, HPV, HBV, and EBV.
The promising results from this Phase 1 trial suggest that SCG101 could potentially transform the treatment landscape for patients with HBV-related HCC, offering a novel approach that addresses both the underlying viral infection and the resulting cancer.
