Recently, the first patient was enrolled and dosed in a Phase III registrational clinical trial at the General Hospital of Pingmei Shenma Medical Group. The trial is for Cafelkibart (LM-108, a CCR8 monoclonal antibody), a Class 1 innovative drug independently developed by LaNova Medicines, a wholly-owned subsidiary of Sino Biopharm (1177.HK). The trial evaluates LM-108 in combination with a PD-1 inhibitor for the second-line treatment of CCR8-positive locally advanced or metastatic gastric cancer/gastroesophageal junction (G/GEJ) adenocarcinoma. LM-108 is the fastest-developing CCR8 monoclonal antibody globally, with global first-in-class (FIC) potential, and is currently undergoing two pivotal registrational clinical trials. 

 

 

Reshaping Anti-Tumor Immune Response, Impressive Preliminary Clinical Data

 

Studies have shown that immunosuppression mediated by regulatory T cells (Tregs) in the tumor microenvironment is one of the key mechanisms leading to immunotherapy failure^{[1, 2]}. LM-108 is an innovative therapy developed based on this mechanism. By targeting the highly expressed CCR8 receptor on the surface of tumor-infiltrating Treg cells with high affinity and selectivity, it precisely eliminates immunosuppressive Treg cells in the tumor microenvironment, thereby reshaping the anti-tumor immune response. 

 

Data from a Phase I/II clinical study of LM-108 combined with toripalimab for the second-line treatment of advanced gastric cancer showed that among the 40 patients who received this combination therapy:

 

● Significant benefit in the overall population: The objective response rate (ORR) reached 32.5%, the disease control rate (DCR) was 67.5%, the median progression-free survival (PFS) was 5.32 months, and the median OS was as long as 22.64 months. 

 

● Precise stratification based on CCR8 expression: Efficacy is highly positively correlated with the level of CCR8 expression. In the CCR8-positive (CCR8≥1) population, the ORR reached 41.4%, and the median OS was 22.64 months. In the advantaged population with high CCR8 expression (CCR8≥2), the ORR was as high as 62.5%, the DCR was 75%, the median PFS was extended to 7.33 months, and the median OS has not yet been reached. 

 

Compared to the current standard treatment of paclitaxel monotherapy (median OS of approximately 7.4-8.4 months), the LM-108 combination regimen significantly prolonged the median OS in the overall population, highlighting its potential breakthrough clinical value. 

Addressing the Dilemma of Second-Line Gastric Cancer Treatment, Providing a New Solution

 

Gastric cancer is one of the most common malignant tumor in China, and most patients are already in the advanced stage at the time of diagnosis. For patients who have experienced treatment failure with first-line therapy, the current second-line standard of care is still dominated by chemotherapy such as paclitaxel or combination targeted therapy, with a median overall survival (OS) of only about 8.4 months. Although PD-1/PD-L1 immunotherapy has made progress in the field of gastric cancer, in the second-line treatment setting, only a small number of patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) can benefit from it. The vast majority of patients still face the severe challenge of primary or secondary drug resistance^[3]. LM-108, in combination with a PD-1 inhibitor, is expected to exert a synergistic enhancing effect, providing a new solution for the second-line treatment of advanced gastric cancer. 

 

Breaking the Bottleneck of Immune Drug Resistance, Granted Two Breakthrough Therapy Designations

 

LM-108 has received two Breakthrough Therapy Designations from the Center for Drug Evaluation (CDE) of the National Medical Products Administration for: combination with toripalimab for advanced solid tumors with MSI-H/dMMR that have experienced disease progression after treatment with immune checkpoint inhibitors; and combination with toripalimab for CCR8-positive advanced G/GEJ adenocarcinoma that has failed previous first-line standard therapy. Currently, a pivotal registrational study for patients with advanced solid tumors with MSI-H/dMMR is also progressing steadily. 

 

Through its innovative mechanism of selectively regulating immunosuppression in the tumor microenvironment, LM-108 not only has the potential to break through the bottleneck of existing immunotherapy drug resistance but is also expected to open up a new immunotherapy path of "targeting Tregs", bringing more precise and effective treatment options to cancer patients in China and around the world. With the advancement of two pivotal registrational studies, LM-108 is expected to become the world's first approved CCR8-targeted therapy. 

 

References:

 

[1] Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy.Cell Res. 2017Jan;27(1):109-118.

[2] Villarreal DO, L'Huillier A, Armington S, et al.Targeting CCR8 Induces Protective Antitumor Immunity and Enhances Vaccine-Induced Responses in Colon Cancer.Cancer Res. 2018 Sep 15;78(18):5340-5348.

[3] Li Juan, Ye Sisi, Han Chun, et al. Efficacy analysis of immune checkpoint inhibitors combined with chemotherapy and anti-angiogenic drugs in the second-line treatment of patients with advanced gastric cancer and gastroesophageal junction adenocarcinoma[J]. Journal of Medical Colleges of PLA, 2023, 44(7):763-768. 

 

Declaration:

 

1. This press release is intended to facilitate the communication and exchange of medical information and is for reference by healthcare professionals only. It is not for advertising purposes. 

2. The company does not recommend any drugs and/or indications. 

3. The information contained in this press release is for reference only and cannot replace professional medical guidance in any way, nor should it be considered as a diagnosis or treatment recommendation. If you wish to understand specific disease diagnosis and treatment information, please follow the advice or guidance of a physician or other healthcare professional. 

 

Forward-Looking Statements:

 

This press release contains certain forward-looking statements, including statements regarding the clinical development plan for [Cafelkibart (LM-108)], expectations of its clinical benefits and advantages, commercialization prospects, the likelihood of clinical benefit for patients, and potential commercial opportunities. Words such as "expect", "believe", "continue", "may", "estimate", "hope", "intend", "plan", "potential", "predict", "project", "should", "will", "propose", and similar expressions are intended to identify forward-looking statements, but not all forward-looking statements contain these identifying words. These forward-looking statements are predictions or expectations made by the company based on currently available data and information, and actual results may differ materially from these forward-looking statements due to uncertainties or risks such as policy, R&D, market, and regulatory factors. Current or potential investors are advised to carefully consider the potential risks and should not place undue reliance on the forward-looking statements in this press release, which contain information only as of the date of this press release. Unless required by law, the company undertakes no obligation to update or revise any forward-looking statements in this press release as a result of new information, future events, or other circumstances.