AbelZeta and AstraZeneca's Armored GPC3 CAR-T Therapy Shows Promising Efficacy in Advanced Hepatocellular Carcinoma, Published in Nature
核心洞察
C-CAR031/AZD7003 (搜索), an autologous GPC3 (搜索)-targeted CAR-T armored with dnTGFβRII (搜索), demonstrated a 44.4% objective response rate in 36 heavily pretreated advanced HCC patients with a median of four prior lines of therapy.
Tumor regression was observed in 32 of 36 patients, with a median best tumor reduction from baseline of 41.6% and median overall survival reaching 14.2 months.
The safety profile was manageable, with only two patients experiencing grade 3 cytokine release syndrome and nine patients having grade 3 or higher non-hematological adverse events.
A first-in-human clinical study evaluating C-CAR031, a novel glypican-3 (GPC3 (搜索))-targeted chimeric antigen receptor T-cell (CAR-T) therapy, has demonstrated a manageable safety profile and encouraging antitumor activity in patients with heavily pretreated advanced hepatocellular carcinoma (搜索) (HCC), according to findings published in Nature. The publication, titled "GPC3-specific dnTGFβRII (搜索)–armoured CAR-T cells for hepatocellular carcinoma," provides an update to preliminary data first presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
The investigator-initiated trial was led by Dr. Tingbo Liang and Dr. Qi Zhang at The First Affiliated Hospital, Zhejiang University School of Medicine, with support from AbelZeta Pharma (搜索), Inc. C-CAR031, now known as AZD7003, is an autologous GPC3 (搜索)-targeting CAR-T therapy designed by AstraZeneca using their dominant-negative transforming growth factor-beta receptor II (dnTGFβRII (搜索)) armoring platform, which is intended to overcome the immunosuppressive tumor microenvironment.
Clinical Efficacy in a Heavily Pretreated Population
The study enrolled 36 patients with advanced HCC who had received a median of four prior lines of treatment. Tumor regression was observed in 32 of 36 patients, with a median best tumor reduction from baseline of 41.6% (range: 3.4–94.4%) in target lesions. The objective response rate (ORR) reached 44.4%, and the median duration of response (DOR) was 4.4 months (95% confidence interval: 2.9–7.4).
Median progression-free survival (PFS) was 4.2 months (95% confidence interval: 2.9–4.8), while median overall survival (OS) was 14.2 months (95% confidence interval: 10.1 to not evaluable).
Safety Profile
The safety data indicated a manageable tolerability profile. Only two patients experienced cytokine release syndrome of grade 3, and nine patients had non-hematological adverse events of grade 3 or higher.
Strategic Collaboration and Development Path
In December 2023, AbelZeta announced an agreement with AstraZeneca to co-develop C-CAR031 in China. In January 2026, the companies expanded their arrangement when AstraZeneca acquired AbelZeta's remaining China development and commercialization rights to C-CAR031. AstraZeneca now solely leads the global development and commercialization of the investigational product under the name AZD7003.
"We would like to express our deepest appreciation to The First Affiliated Hospital, Zhejiang University School of Medicine's Dr. Liang and Dr. Zhang, as well as the outstanding clinical team for conducting this landmark study with exceptional scientific rigor," said Tony (Bizuo) Liu, Chairman and Chief Executive Officer of AbelZeta. "We are especially grateful to the patients and their families who participated in this trial, whose courage and trust made this important research possible."
Liu further noted, "We are delighted to have collaborated with AstraZeneca on C-CAR031/AZD7003 (搜索) and are honored to see the clinical data in hepatocellular carcinoma (搜索) published in Nature. Reaching this milestone is testament to our complementary cell therapy capabilities."