Shanghai Fosun Pharmaceutical (Group) Co., Ltd (SHA: 600196, HKG: 2196) has announced the initiation of a Phase II clinical study in China for HLX26, an in-house developed lymphocyte activation gene 3 (LAG-3, aka CD233) inhibitor, in combination with its programmed-death 1 (PD-1) inhibitor HaiSiZhuang (serplulimab) for the treatment of metastatic colorectal cancer (mCRC). This study focuses on the regimen’s use as a fourth-line treatment option for patients.
Understanding the Mechanism of Action of LAG-3 Inhibition
LAG-3 is a complex-binding immunoassay receptor that activates effector T cell activity while inhibiting T reg activity, sharing a similar mechanism of action to that of PD-1 inhibition. Primarily expressed on activated T cells and some NK cells, LAG-3 has a negative regulatory effect on T cell proliferation, activation, and homeostasis. By inhibiting LAG-3, it is possible to reactivate T cells and restore their ability to target and kill tumor cells.
Serplulimab’s Global Clinical Studies and Approvals
Serplulimab has been approved in China for the treatment of unresectable or metastatic microsatellite highly unstable (MSI-H) solid tumors that have failed standard therapy, squamous non-small cell lung cancer (sqNSCLC), and extensive stage small cell lung cancer (ES-SCLC). The drug is a central component in multiple global clinical studies, including eleven different combination therapies. A market filing for serplulimab combined with cisplatin plus fluorouracil (5-FU) for first-line locally advanced/recurrent or metastatic esophageal squamous cell carcinoma (ESCC) has been accepted for review by the NMPA.
Ongoing Studies for HLX26 in Solid Tumors and Lymphoma
HLX26 is currently undergoing a Phase I study in solid tumors and lymphoma, as well as a Phase I study in combination with serplulimab in solid tumors. Additionally, the HLX26/serplulimab combination has previously been cleared for a Phase II study in NSCLC in China, indicating the potential synergistic effects of this dual immunotherapy approach in cancer treatment.-Fineline Info & Tech
