SBP GROUP (01177): The first patient has been enrolled in the second-line treatment clinical trial of gastric cancer stage III with Crechiquibab monoclonal antibody "CCR8 monoclonal antibody".

SBP Group (01177) announced that its wholly-owned subsidiary, Lexin Pharmaceutical Technology (Shanghai) Co., Ltd. (Lexin Pharmaceutical), has successfully completed the enrollment of the first patient in the Phase III registration clinical trial for the nationally classified innovative drug CCR8 monoclonal antibody "LM-108" (research code: LM-108) in combination with PD-1 inhibitor as second-line treatment for locally advanced or metastatic gastric cancer/gastroesophageal junction (G/GEJ) adenocarcinoma that is CCR8 positive. This study is the second key registration clinical trial conducted for LM-108. LM-108 is a potential globally first-in-class CCR8 monoclonal antibody, and currently the only CCR8-targeted drug that has been granted breakthrough therapy designations by the China National Medical Products Administration Drug Evaluation Center (CDE) for two breakthrough therapy designations: 1) in combination with pembrolizumab for the treatment of microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) advanced solid tumors following treatment with immune checkpoint inhibitors; 2) in combination with pembrolizumab for CCR8 positive advanced G/GEJ adenocarcinoma that has failed standard first-line treatment. In a Phase I/II study of LM-108 in combination with pembrolizumab for second-line treatment of advanced gastric cancer, the combination showed excellent anti-tumor activity and good safety. Preliminary data showed that among 40 gastric cancer patients receiving LM-108 in combination with pembrolizumab as second-line treatment: Benefit was significant for the entire population: objective response rate (ORR) was 32.5%, disease control rate (DCR) was 67.5%, median progression-free survival (PFS) was 5.32 months, and median overall survival (OS) was as long as 22.64 months. Stratification based on CCR8 expression: Efficacy was highly positively correlated with CCR8 expression level. In the CCR8 positive population (CCR81), ORR was 41.4%, and median OS was 22.64 months; in the subset with high CCR8 expression (CCR82), ORR was even higher at 62.5%, DCR was 75%, PFS was extended to 7.33 months, and median OS was not yet reached. Compared to current standard treatment with paclitaxel monotherapy (median OS approximately 7.4-8.4 months), the LM-108 combination achieved significant survival benefits in the entire population, extending median OS to 22.64 months, demonstrating breakthrough clinical value. Gastric cancer is one of the high incidence malignant tumors in China, with most patients being diagnosed at late stages and overall prognosis being poor. For patients who fail first-line treatment, current second-line standard treatments primarily involve chemotherapy with paclitaxel or combination targeted therapy, with limited clinical benefits. PD-1/PD-L1 immunotherapy in second-line gastric cancer only benefits a small number of MSI-H/dMMR patients, with most patients still facing issues of primary or acquired resistance. Studies have shown that regulatory T cells (Tregs) in the tumor microenvironment mediate immune suppression, which is one of the key mechanisms leading to the failure of immune therapy. The CCR8 monoclonal antibody selectively targets the CCR8 receptor highly expressed on the surfaces of tumor-infiltrating Treg cells with high affinity and selectivity, selectively eliminating immunosuppressive Treg cells in the tumor microenvironment, reshaping anti-tumor immune responses. Its combination with PD-1 inhibitors is expected to produce a strong synergistic effect, providing a new solution for second-line treatment of advanced gastric cancer. Currently, another key registration clinical trial for LM-108 targeting MSI-H/dMMR advanced solid tumors is also progressing steadily, with the potential to become the world's first approved CCR8-targeted therapy. Its innovative mechanism of selectively regulating immunosuppression in the tumor microenvironment not only has the potential to break through the resistance bottleneck of existing immune therapy, but also may open up a new path for targeted Treg immunotherapy, providing more precise and effective treatment options for cancer patients in China and globally.