CHS-114

Overview

CHS-114 (formerly SRF114) is an investigational, afucosylated human IgG1 monoclonal antibody that targets chemokine receptor 8 (CCR8), a receptor enriched on regulatory T cells (Tregs) within the tumor microenvironment. The program originated at Surface Oncology (SRF114) and was acquired by Coherus BioSciences in September 2023; it is being evaluated in a first‑in‑human Phase 1 study (NCT05635643) as monotherapy and in combination with the anti–PD‑1 antibody toripalimab. (globenewswire.com)

Mechanism of action

• Target: CCR8 on tumor‑infiltrating Tregs. Human and animal studies show CCR8 is selectively or preferentially expressed on intratumoral Tregs versus peripheral T cells, supporting CCR8 as a Treg‑depleting target to relieve tumor immunosuppression. (pnas.org)
• Drug design: CHS‑114 is an afucosylated anti‑CCR8 antibody intended to deplete CCR8+ Tregs via enhanced Fc‑mediated cytotoxicity/phagocytosis (ADCC/ADCP), aiming to spare peripheral Tregs and preserve effector CD8+ T cells. Preclinical work with SRF114 demonstrated Treg depletion, pro‑inflammatory remodeling of the tumor microenvironment, and antitumor activity, including synergy with PD‑1 blockade. (globenewswire.com)

Additional literature supports the biological rationale for CCR8 Treg targeting across tumor types (e.g., ovarian, colorectal, lung), showing selective intratumoral expression and antitumor effects when CCR8+ Tregs are depleted. (translational-medicine.biomedcentral.com)

Clinical development

• Trial: NCT05635643 is a Phase 1, open‑label, dose‑escalation/optimization and expansion study of CHS‑114 as monotherapy and with toripalimab in advanced solid tumors, including dedicated cohorts in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). (clinicaltrials.stanford.edu)
• Conference presentations: Preliminary dose‑escalation results were presented at ASCO 2024; interim dose‑expansion data in HNSCC were presented at AACR 2025; a SITC 2025 poster is planned. (ascopubs.org)

Efficacy

• ASCO 2024 (dose‑escalation, monotherapy): In 19 evaluable patients, no objective responses had been observed at the time of reporting; stable disease rate was 47% (company summary). The abstract (data cutoff December 15, 2023; 15 treated) focused on pharmacokinetics and pharmacodynamics without reporting responses. (investors.coherus.com)
• AACR 2025 (dose‑optimization/expansion in HNSCC with toripalimab): Interim data included a confirmed partial response in a heavily pretreated, PD‑1–refractory patient, along with intratumoral pharmacodynamic changes (>50% depletion of CCR8+ Tregs and increased CD8+ T cells). The AACR abstract (CT038) describes the Phase 1 study design; the numerical response dataset beyond the single confirmed PR has not been fully detailed publicly. (nasdaq.com)

Interpretation: Early human data demonstrate proof of mechanism (Treg depletion and CD8+ T‑cell increase) and an initial signal of activity in combination with PD‑1 blockade in HNSCC; robust response‑rate data are not yet available.

Safety

• ASCO 2024 (monotherapy): No dose‑limiting toxicities were reported up to 700 mg; treatment‑related adverse events occurred in 33% (all Grade 1–2), most commonly pyrexia. One treatment‑related serious adverse event of Grade 2 colitis was noted in broader company reporting. Pharmacokinetics were approximately dose‑proportional with an estimated half‑life of ~9–17 days. (ascopubs.org)
• AACR 2025 (combination with toripalimab in HNSCC): Safety was described as manageable and consistent with advanced disease and toripalimab’s known profile; detailed incidence tables have not been released. (nasdaq.com)

Overall, the emerging safety profile appears acceptable in early Phase 1 experience, with ongoing dose optimization to refine the recommended doses for expansion. (investors.coherus.com)

Further reading

• ASCO 2024 abstract (J Clin Oncol): Preliminary first‑in‑human results of CHS‑114 monotherapy (NCT05635643). (ascopubs.org)
• AACR 2025 abstract (Cancer Research, CT038): Phase 1 study of CHS‑114 with/without toripalimab in advanced solid tumors. (aacrjournals.org)
• Coherus news (AACR 2025): Early HNSCC combination data and intratumoral pharmacodynamics. (nasdaq.com)
• Preclinical rationale for SRF114/CHS‑114 (AACR 2023): Anti‑CCR8 depletes tumor Tregs and reshapes the TME. (globenewswire.com)
• Background on CCR8 in tumor Tregs: PNAS 2022; Journal of Translational Medicine 2024 (CRC); J Transl Med 2023 (ovarian). (pnas.org)

Notes: Data are interim and primarily from conference abstracts and company communications as of April–October 2025; mature, peer‑reviewed clinical efficacy results (e.g., objective response rates across cohorts) have not yet been published. (ascopubs.org)

Last updated: Oct 2025