Coherus Unveils Phase I Dose Escalation Study Results of CCR8 Antibody CHS-114 at 2024 ASCO Meeting

Coherus BioSciences, Inc. has announced promising preliminary results from the Phase 1 study of CHS-114, a novel afucosylated human immunoglobulin G1 (IgG1) monoclonal antibody. This antibody selectively targets the CCR8 receptor, which is predominantly expressed on tumor-infiltrating regulatory T cells (Tregs). By targeting CCR8, CHS-114 aims to reduce immune suppression in the tumor microenvironment (TME) without broadly depleting Treg cells, which could otherwise lead to autoimmune activation.

Initial data from the dose escalation phase of the study were presented at the ASCO Annual Meeting, highlighting the safety and pharmacokinetic profile of CHS-114. The study involved heavily pretreated patients with advanced solid tumors. The results showed no dose-limiting toxicities (DLTs) and generally low-grade treatment-emergent adverse events (TEAEs). Notably, one patient experienced a Grade 2 colitis as a serious adverse event (SAE), but there were no treatment-related adverse events leading to discontinuation or death.

The pharmacokinetic analysis of CHS-114 indicated a dose-proportional exposure and a linear elimination with a half-life ranging between 9 to 17 days. Importantly, the study achieved proof of mechanism by demonstrating selective depletion of peripheral CCR8+ Treg cells, maintained throughout the dosing interval.

Dr. Rosh Dias, Chief Medical Officer at Coherus, emphasized the significance of these results, noting that targeting CCR8 could potentially overcome Treg-mediated immune suppression within the TME. This mechanism may facilitate T cell recruitment, converting 'cold' tumors into 'hot' ones, thereby enhancing anti-tumor activity when combined with other immuno-oncology (IO) agents. The data supports further evaluation of CHS-114 in combination with Coherus' anti-PD-1 antibody, toripalimab, and other IO agents.

The Phase 1 trial, designated SRF114-101, is a first-in-human, open-label, dose escalation study evaluating CHS-114 both as a monotherapy and in combination with toripalimab. The study enrolled patients with advanced solid tumors, the majority of whom had undergone multiple prior treatments. The trial utilized a Bayesian optimal interval (BOIN) design, including accelerated titration and a 3+3 run-in phase. Stage 1b of the study will include additional patients with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC).

The primary endpoints of the trial are the rates of DLTs and TEAEs, with the aim of determining two recommended doses for future studies. Secondary endpoints include the objective response rate (ORR) based on RECIST v1.1 criteria and various pharmacokinetic and pharmacodynamic assessments. An exploratory endpoint will assess changes in the frequency of CCR8-expressing immune cell subsets in the periphery.

CHS-114 has shown potential in preclinical studies, demonstrating antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) to deplete tumoral CCR8+ Tregs. In combination with anti-PD-1 treatment, CHS-114 enhanced anti-tumor activity in murine models. These findings support its continued evaluation in clinical trials for various advanced solid tumors, including head and neck cancer.

Coherus BioSciences is a commercial-stage biopharmaceutical company focused on developing innovative cancer therapies. Its immuno-oncology pipeline aims to enhance both innate and adaptive immune responses, potentially improving outcomes for cancer patients. Alongside CHS-114, their pipeline includes other promising candidates such as casdozokitug and CHS-1000, targeting different mechanisms of immune suppression.

Overall, the preliminary results for CHS-114 are encouraging, providing a solid foundation for further investigation in combination therapies aimed at improving cancer treatment outcomes.