Coherus Biosciences presents data from Phase 1 dose expansion study of CHS-114

Coherus announced data from its ongoing Phase 1 clinical trial evaluating CHS-114, a selective, cytolytic anti-CCR8 antibody, as monotherapy and in combination with toripalimab in patients with recurrent/metastatic head and neck squamous cell carcinoma evaluating two pharmacologically active doses of CHS-114 for dose optimization. These data are being presented at the 2025 American Association for Cancer Research Annual Meeting, taking place April 25-30, in Chicago, Illinois. The data showed a confirmed partial response in a heavily pretreated PD-1 refractory patient, a greater than 50% depletion in CCR8+ Treg, and an increase in CD8+ T cells, consistent with anti-tumor activity and demonstrating proof of mechanism. Importantly, the safety profile was consistent with advanced disease and the known safety profile of toripalimab. These data support continued evaluation of CHS-114 in combination with other therapies, including toripalimab. Results support advancement and ongoing enrolment in Part 3 of the study evaluating CHS-114 with toripalimab in HNSCC. CHS-114 is an afucosylated CCR8 monoclonal antibody and is the only known selective molecule designed to exclusively target human CCR8 with no off-target binding and preferentially kills CCR8+ Tregs within the tumor microenvironment while preserving CD8+ effector T cells and Tregs in normal tissue. This open-label Phase 1b clinical trial evaluated CHS-114 as a single-agent and in combination with toripalimab in 21 patients with advanced solid tumors including HNSCC. Patients received either CHS-114 alone or in combination with toripalimab q3w. The primary endpoint of the study was to determine dose limiting toxicities and treatment emergent adverse events, with the goal of identifying two recommended doses for expansion. Key secondary endpoints included objective response rate based on investigator review per RECIST v1.1 as well as pharmacokinetics and pharmacodynamics. As of the data cutoff date of January 24, 2025: CHS-114 monotherapy demonstrated Treg cell depletion, and significant increase in CD8+ T cells in the tumor, establishing proof of mechanism and confirming the doses are pharmacologically active. CHS-114 with toripalimab had promising antitumor activity in HNSCC that warrants continued exploration. CHS-114 administration leads to a substantial increase in CD8+ T cells in the tumor microenvironment, providing a strong rationale for combining with toripalimab and other drugs such as T cell engagers and bispecifics. A confirmed partial response was achieved in the high dose cohort of CHS-114 in combination with toripalimab in a heavily pre-treated PD-1 refractory patient, demonstrating CHS-114 in combination with toripalimab can potentially overcome PD-1 resistance. CHS-114 with and without toripalimab had a manageable safety profile in HNSCC patients, with TEAEs consistent with advanced disease and the known safety profile of toripalimab. Two CHS-114 doses were selected for dose optimization based on safety, peripheral CCR8+ Treg depletion, PK and biomarker data. These results support continued evaluation of CHS-114 in combination with other drugs including toripalimab, with broad potential applications in many solid tumors with a high density of CCR8+ Treg cells. A second-line HNSCC dose optimization study of CHS-114 in combination with toripalimab in HNSCC and gastric cancer patients is ongoing, with anticipated results in 1H26. The current study design is expected to address the regulatory requirements under Project Optimus1 and support the recommendation of a phase 2 dose by early 2026.