Coherus BioSciences presented promising early clinical data from its ongoing Phase 1 trial evaluating CHS-114, a selective cytolytic anti-CCR8 antibody, at the 2025 American Association for Cancer Research (AACR) Annual Meeting in Chicago. The study assessed CHS-114 both as monotherapy and in combination with the PD-1 inhibitor toripalimab in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
The data revealed a confirmed partial response in a heavily pretreated PD-1 refractory patient with low PD-L1 expression, suggesting the combination therapy may potentially overcome resistance to PD-1 inhibitors. Additionally, the treatment demonstrated significant depletion of CCR8+ regulatory T cells (Tregs) ranging from 52-97%, along with a substantial increase in CD8+ T cells in the tumor microenvironment.
"The data to date demonstrate a robust depletion of Treg cells in tumors, with a manageable safety profile, and a patient with a meaningful clinical response, which is highly encouraging," said Rosh Dias, M.D., Coherus' Chief Medical Officer. "Furthermore, the profound increase in CD8+ T cells, making these tumors immunologically hot, is exciting as it supports CHS-114 being combined with several treatment modalities including T Cell Engagers."
Study Design and Key Findings
The 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 (240 mg) administered every three weeks.
Key findings from the study as of January 24, 2025, include:
- CHS-114 monotherapy demonstrated significant Treg cell depletion (52-97%) and increased CD8+ T cells in tumors
- The combination of CHS-114 with toripalimab showed promising antitumor activity in HNSCC
- A confirmed partial response was achieved in the high-dose cohort of the combination therapy in a heavily pretreated PD-1 refractory patient
- Both monotherapy and combination therapy demonstrated manageable safety profiles
- Two CHS-114 doses were selected for further optimization based on safety, peripheral CCR8+ Treg depletion, and biomarker data
Douglas Adkins, M.D., Professor of Medicine and Director of Head and Neck and Thyroid Medical Oncology at Washington University School of Medicine, commented on the significance of these findings: "One of the biggest challenges in oncology has been finding a treatment that depletes Treg cells and relieves immune suppression in the tumor without causing collateral autoimmune disease or affecting antitumor T cells. These early clinical results are exactly what we've been hoping for and demonstrate CHS-114's ability to remodel the tumor microenvironment in favor of anti-tumor activity."
Mechanism of Action and Potential Applications
CHS-114 is an afucosylated CCR8 monoclonal antibody designed to selectively target human CCR8 with no off-target binding. It preferentially kills CCR8+ Tregs within the tumor microenvironment while preserving CD8+ effector T cells and Tregs in normal tissue, potentially avoiding the autoimmune side effects that have limited other immunotherapies.
In preclinical studies, CHS-114 induced antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP) to deplete tumoral CCR8+ Tregs. Treatment with CHS-114 alone reduced tumor growth in murine models, with enhanced antitumor activity observed when combined with anti-PD-1 treatment.
Dr. Dias emphasized that while head and neck cancer is a strategic focus for Coherus, CHS-114 has potential applications in many solid tumors with high densities of CCR8+ Treg cells, including non-small cell lung cancer and colorectal cancer.
Future Development Plans
Based on these promising results, Coherus is continuing enrollment in Part 3 of the study, which is evaluating CHS-114 with toripalimab in 40 patients with second-line HNSCC. Additionally, a second-line Phase 1 dose optimization study of the combination in HNSCC and gastric cancer patients is ongoing, with results anticipated in the first half of 2026.
The current study design is expected to address regulatory requirements under Project Optimus and support the recommendation of a Phase 2 dose by early 2026.
The data were presented at AACR 2025 by lead author Francis Worden, M.D., from the University of Michigan, in a poster session on Phase 0 and Phase 1 Clinical Trials. Coherus also hosted an investor and analyst call featuring study investigator Dr. Douglas Adkins to discuss the findings.
These early clinical results provide a strong rationale for combining CHS-114 with toripalimab and potentially other immunotherapies, offering a new approach to overcome resistance to existing treatments and potentially expanding treatment options for patients with difficult-to-treat solid tumors.
