LY011 is a third-generation CAR-T product independently developed by Shanghai Longyao Biotechnology Co., Ltd. on the OX40 platform. It is a chimeric antigen receptor T cell (CAR-T) targeting CLDN18.2 using a lentiviral vector. This project targets solid tumor therapy. In the Affiliated Hospital of Xuzhou Medical University, President Song Jun and Director Fei Sujuan led respectively, and carried out an IIT (Investigator Initiated Trial) study on the treatment of gastric cancer and pancreatic cancer.
This project plans to enroll about 12-18 patients with CLDN18.2 positive advanced malignant solid tumors (gastric cancer, pancreatic cancer and ovarian cancer, etc.). As of January 31, 2021, the project has completed the DLT observation and efficacy evaluation after the first treatment of 4 patients with advanced malignant solid tumors (3 gastric cancer and 1 pancreatic cancer). According to the RECIST1.1 evaluation criteria, 2 out of 4 subjects had the best response to disease remission (PR), and 2 subjects had stable disease (SD). The overall objective response rate (ORR) at this stage was 50.0% (2/4), and the overall disease control rate (DCR) was 100% (4/4). Among them, in the lowest dose group of 1×106 CART Cells/kg, the objective response rate was 66.67% (2/3), and the disease control rate was 100% (3/3).
To date, no serious adverse events or adverse events leading to subject dropout have been identified. The majority of adverse events reported were mild and moderate. 3 of 4 subjects experienced cytokine release syndrome (CRS) after CAR-T cell reinfusion, grade I, with only fever; CAR-T cell-related encephalopathy was not reported syndrome (CRES). No specific safety concerns were identified with respect to vital sign data (respiration, pulse, systolic blood pressure, diastolic blood pressure, temperature), ECOG score, and physical examination data at each visit.
At present, LY011 injection has no unexpected adverse reactions (SUSAR) and special safety problems, and the above-mentioned study dose of LY011 injection is safe and well tolerated in subjects with advanced malignant solid tumors. In addition, through the current research, the PK characteristics of different doses of LY011 injection in subjects with advanced malignant solid tumors have been mastered, and its anti-tumor effect has been preliminarily demonstrated.
Based on the results of safety, PK characteristics and preliminary efficacy studies, it is believed that LY011 injection is worthy of further research and development.
The OX40 parallel co-stimulatory signaling technology independently developed by Longyao Bio can reduce T cell exhaustion, enhance the proliferation and killing ability of CAR-T cells, and make it release more effectors, thereby improving the safety and efficacy of CAR-T cells. -T performance.
Company Profile:
Shanghai Longyao Biotechnology Co., Ltd. is a world-leading immune cell drug research and development enterprise with independent intellectual property rights. Its controlling shareholder is China Biotechnology Services Holdings Limited, a Hong Kong-listed company.
The company has a research and development team with Professor Yang Xuanming of Shanghai Jiaotong University as the core. There are more than ten cell-based drugs under development for the treatment of leukemia, lymphoma, pancreatic cancer, glioma and other diseases that greatly affect people's health. Among them, the CD20-CART-OX40 product was officially approved by China on January 20, 2021. It is a national first-class new drug, and it is the only CD20-targeted CAR-T product in China that has also entered clinical registration.