Tagmokitug (CCR8)
A potentially best-in-class anti-CCR8 cytolytic antibody.
Tagmokitug (formerly known as CHS-114) is a highly selective antibody-dependent cellular cytotoxicity (ADCC)-enhanced anti-CCR8 antibody currently in a Phase 2 study and Phase 1b studies in combination with toripalimab in patients with advanced solid tumors.
Target
CCR8 is a chemokine receptor predominantly expressed by tumor infiltrating regulatory T cells (Tregs) that suppress the body’s anti-tumor immune response. Targeting CCR8 is a promising potential therapeutic strategy designed to selectively deplete tumor resident Tregs, reshape the tumor microenvironment and enhance anti-tumor immune response.
Tagmokitug is an antibody that has the potential to specifically target and remove CCR8+ Treg cells in the tumor environment, promoting effector T cells in tumors and leaving Tregs in normal tissue unaffected.
Program
Tagmokitug is a human, afucosylated anti-CCR8 antibody designed to selectively target human CCR8 and preferentially deplete CCR8+ Treg cells within the tumor microenvironment and not effector T (Teff) cells in tumors or Tregs in normal tissue. In preclinical studies, tagmokitug induced ADCC and/or antibody-dependent cellular phagocytosis (ADCP) pathways to deplete tumoral Treg cells. In addition, tagmokitug reduced tumor growth in murine models.
Progress
Early clinical data from an ongoing Phase 1 clinical trial evaluating tagmokitug as monotherapy and in combination with toripalimab in patients with recurrent/metastatic HNSCC was reported at AACR 2025 The data showed a confirmed partial response in a heavily pre-treated PD-1 refractory patient, a 50% depletion in CCR8+ Treg, and an increase in CD8+ T cells, consistent with anti-tumor activity, demonstrating proof of mechanism. The safety profile was consistent with advanced disease and the known safety profile of toripalimab.
Tagmokitug is currently being evaluated in combination with toripalimab in a Phase 2a study in patients with colorectal cancer and Phase 1b studies in patients with advanced solid tumors, including second-line head and neck squamous cell carcinoma, second-line gastric cancer and first-line and second-line esophageal cancer.
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