Rockville, Maryland, United States, November 9, 2026
AbelZeta Inc. has announced updated clinical results from its first-in-human Phase I study evaluating C-CAR031, also known as AZD7003, an investigational glypican-3 (GPC3)-targeted armored autologous chimeric antigen receptor T-cell (CAR-T) therapy for patients with advanced hepatocellular carcinoma (HCC). The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain, highlighting encouraging antitumor activity, disease control and survival outcomes in heavily pretreated patients. The study evaluated 36 individuals with advanced liver cancer who had received a median of four previous lines of systemic therapy. According to the company, the updated analysis demonstrated a confirmed overall response rate of 44.4% and a disease control rate of 91.7% across all four dose levels. At the recommended Phase II dose, the disease control rate reached 100%, with an estimated 12-month overall survival rate of 75.6%. These findings provide additional clinical evidence supporting the investigation of engineered CAR-T therapies in solid tumors, an area where achieving durable treatment responses remains challenging.
Phase I Trial Demonstrates Encouraging Antitumor Activity
The updated results were presented during a rapid oral presentation at ESMO Congress 2026 on October 26, under abstract number 1680RO. The clinical study included 36 patients with advanced hepatocellular carcinoma, most of whom had extensive disease and limited remaining treatment options. Approximately 94.4% of participants had Barcelona Clinic Liver Cancer (BCLC) Stage C disease, while 83.3% had extrahepatic lesions, indicating that their cancer had spread beyond the liver. Furthermore, 91.7% had previously received both immunotherapy and vascular endothelial growth factor (VEGF) or VEGF receptor-targeting treatments. As of the August 15, 2026 data cutoff, the median follow-up period was 14.9 months. The confirmed overall response rate was 44.4%, indicating that this proportion of patients experienced a confirmed reduction in tumor burden according to the study’s response criteria. The disease control rate reached 91.7%, including patients who achieved partial responses or stable disease. Previously reported imaging findings also showed tumor regression in 32 of 36 participants (88.9%), involving both intrahepatic and extrahepatic lesions. At the recommended Phase II dose of 2.5 million CAR-T cells per kilogram, the disease control rate was 100%, with a 12-month overall survival rate of 75.6%. These early findings are encouraging, although the small study population and absence of a randomized control group mean that further clinical evaluation is necessary.
Engineered CAR-T Technology Targets GPC3 and Tumor Resistance
C-CAR031, now known as AZD7003, is an investigational autologous GPC3-targeted armored CAR-T therapy designed to recognize and attack cancer cells expressing glypican-3, a protein frequently found at elevated levels in hepatocellular carcinoma. The treatment uses a patient’s own T cells, which are collected and genetically engineered to express a chimeric antigen receptor capable of recognizing GPC3 on tumor cells. A key feature of the therapy is its incorporation of a dominant-negative transforming growth factor-beta receptor II (dnTGFβRII). This engineered component is intended to help CAR-T cells resist the immunosuppressive effects of transforming growth factor-beta (TGF-β) within the tumor microenvironment. Overcoming tumor-associated immune suppression is a major challenge in developing CAR-T therapies for solid cancers, where the surrounding tumor environment can limit immune-cell activity. The technology was designed by AstraZeneca using its dnTGFβRII armoring platform, while AbelZeta contributed cell therapy engineering, manufacturing and clinical development capabilities. The first-in-human clinical study was conducted at The First Affiliated Hospital of Zhejiang University School of Medicine in China, under the leadership of Professor Tingbo Liang and Dr. Qi Zhang.
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Safety Findings and Global Clinical Development
The updated safety analysis showed that most patients experienced Grade 1 or Grade 2 cytokine release syndrome (CRS), a common inflammatory reaction associated with CAR-T cell therapies. Two patients (5.6%) treated at the highest dose level experienced Grade 3 CRS. No dose-limiting toxicities, immune effector cell-associated neurotoxicity syndrome (ICANS) or immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) were observed. However, interstitial lung disease (ILD) was reported in two patients (5.6%) at the highest dose level, highlighting the importance of continued safety monitoring. The findings indicate a manageable safety profile in this early-stage study, but larger trials will be required to characterize the treatment’s risks more fully. In January 2026, AstraZeneca acquired AbelZeta’s remaining development and commercialization rights to C-CAR031 in China, giving AstraZeneca sole worldwide rights to develop, manufacture and commercialize the investigational therapy. AbelZeta remains eligible for development, regulatory and commercial milestone payments, as well as royalties under the agreement. The program’s continued development under AstraZeneca’s global leadership represents an important step toward evaluating the therapy in a broader clinical setting. The updated Phase I results represent an encouraging milestone for engineered cell therapy research in advanced liver cancer. AZD7003’s antitumor activity and disease control findings support further investigation of GPC3-targeted armored CAR-T therapy in patients with difficult-to-treat hepatocellular carcinoma. Further clinical studies will be essential to establish its long-term efficacy, safety and potential role in oncology treatment.
Source: AbelZeta press release
