The median progression-free survival was 11 months and the SCG101 was well-tolerated.
SCG101 monotherapy, a first-in-class autologous HBsAg-specific T-cell receptor-T cell therapy, demonstrated significant antiviral and antitumor activity in subjects with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).1
Follow-up data on SCG101, from a phase 1/2 trial (NCT05417932) evaluating the therapy, were presented on at The Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting, held November 1-5 in San Diego, California, by Xueshuai Wan, MD, Peking Union Medical College, Beijing, China.
“Hepatitis 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, ”Wan and colleagues wrote.1 “SCG10... has demonstrated high affinity, avidity, and profound antiviral and antitumor functionalities in preclinical studies.”
The trial has enrolled 6 participants with advanced HBV-related HCC that were HBsAg-positive and HBeAg-negative, with the HLA-A*02:01 allele and with cancer Barcelona Clinic Liver Cancer stage B or C. Participants had to have received 1 to 3 prior therapies and at least 12 months of antiviral treatment Entecavir and/or Tenofovir. The participants received a single dose of 5x107 or 1x108 cells/kg SCG101 intravenously after lymphodepletion. The trial evaluated SCG101’s safety, pharmacokinetics, antiviral, and antitumor activities.1
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“SCG101, 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,” Wan and colleagues wrote.1 “A phase 1/2 clinical trial to further evaluate the safety and efficacy of SCG101 is ongoing.”
Investigators found that the transferred T cells exhibited significant dose-dependent proliferation and demonstrated strong persistence during follow-up. All 6 participants experienced antiviral activity after SCG101 infusion as well as drops in serum HBsAg and transient alanine aminotransferase elevations correlating with HBsAg reductions. Four participants experienced a reduction of >1 log from baseline and had disease control, with 2 partial responses and 2 cases of stable disease. The remaining 2 patients did not respond. The median progression-free survival was 11 months. SCG101 was well-tolerated, and investigators observed no dose-limiting toxicity or neurotoxicity.1
"Tumor microenvironment plays a critical role in limiting the response to cancer immunotherapy. Targeting and clearance of HBsAg+ hepatocytes and HBV integrated premalignant dysfunctional cells would significantly contribute to SCG101 T cell stimulation and expansion before entering the hostile tumor microenvironment as well as modulating the immunosuppressive environment in the liver," said Ke Zhang, PhD, chief scientific officer, SCG Cell Therapy, said in a statement on earlier data from the trial.2 "This unique property of SCG101 can effectively overcome a common challenge of T cell therapy, particularly for solid tumors.”
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