CHS-114 shown to have an acceptable safety profile with no dose-limiting toxicities (DLTs) in heavily pretreated patients with solid tumors

Selective depletion of peripheral CCR8+ regulatory T cells (Tregs) was observed and depletion was maintained over the dosing interval, establishing proof of mechanism

Preclinical data and preliminary clinical results support further evaluation of CHS-114 in combination with the anti-programmed cell death protein 1 (PD-1) antibody, toripalimab-tpzi, and other immuno-oncology (IO) agents

REDWOOD CITY, CA, USA I May 23, 2024 I Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), today announced clinical data from the CHS-114, single agent dose escalation stage of its Phase 1 study at the ASCO Annual Meeting, taking place May 31 to June 4, 2024, at McCormick Place in Chicago. CHS-114 is a novel afucosylated human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that selectively and potently targets human CCR8 with no off-target binding. CCR8 is a G protein-coupled receptor (GPCR) that shows preferential expression on tumor resident Treg cells and has promise as a drug target for selectively targeting immune suppression in the tumor microenvironment (TME) without broadly depleting Treg cells, which has the known unwanted side effect of autoimmune activation.

“The Phase 1 preliminary dose escalation results are an important milestone as we progress our innovative I-O pipeline. We are very pleased with the safety profile, the predictable dose proportional pharmacokinetic profile, and the selective depletion of peripheral CCR8+ Tregs that were observed,” said Rosh Dias, M.D., Coherus’ Chief Medical Officer. “By targeting CCR8, we believe CHS-114 has the potential to overcome Treg immune suppression in the TME and allows T cell recruitment, which turns cold tumors hot and enhances anti-tumor activity when combined with I-O agents. The data support further evaluation of CHS-114 in combination treatment with our anti-PD-1 antibody, toripalimab, and other I-O agents.”

CCR8 is a chemokine receptor predominantly expressed by tumor infiltrating Tregs that suppress the body’s natural anti-cancer immune response. Targeting CCR8 is a promising potential therapeutic strategy designed to selectively deplete intratumoral CCR8+ Tregs, reshape the tumor microenvironment by alleviating local immunosuppression, and enhance anti-tumor immune response when combined with I-O agents. Data presented at ASCO demonstrate proof of mechanism for selective depletion of CCR8+ Tregs and an acceptable safety profile to date.

Poster presentation:

Abstract # 2664: Preliminary Results of a Phase 1, First-in-human, Dose Escalation Study of the Anti-CCR8 Cytolytic Antibody, CHS-114 (formerly SRF114) in Patients with Advanced Solid Tumors.
Poster Session: Developmental Therapeutics – Immunotherapy
Date and Time: Saturday, June 1, 2024, 9:00 a.m. – 12:00 p.m. Central Daylight Time

Poster presentation data are summarized as follows:

  • CHS-114 has demonstrated an acceptable safety profile in 20 evaluable, heavily pre-treated patients with advanced solid tumors, with no DLTs reported to date. Treatment emergent adverse events (TEAEs) were generally low grade. One patient experienced a treatment-related serious adverse event (SAE) of Grade 2 colitis. There were no treatment related adverse events (AEs) leading to discontinuation or death.
  • CHS-114 PK exposure was approximately dose proportional, and the elimination appeared linear with a half-life of about 10 days (range 9-17 days).
  • Depletion of peripheral CCR8+ Treg cells was observed and depletion was maintained over the dosing interval, establishing proof of mechanism.
  • Preliminary results and acceptable safety profile support further evaluation of CHS-114 in combination treatment with toripalimab and other I-O agents. In 19 patients evaluable for response, no objective responses were yet noted, while the stable disease rate was 47%.

About the Phase 1 trial (NCT05635643):

SRF114-101 is a Phase 1, First-In-Human, open-label, dose escalation study, evaluating CHS-114 as a single agent and in combination with toripalimab. The study enrolled patients with advanced solid tumors who received more than one line of prior treatment (75% had more than three prior lines). Stage 1a of the study included CHS-114 administered intravenously (IV) on day one of each Q3W cycle as part of single-agent dose escalation and employed the Bayesian optimal interval (BOIN) design, including accelerated titration and 3+3 run-in. Stage 1b will enroll an additional five patients with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) at each of two dose levels.

Primary endpoints: rate of DLTs and TEAEs, with the overarching objective of determining two recommended doses for expansion (RDE).

Key secondary endpoints: objective response rate (ORR) based on Investigator review per RECIST v1.1, pharmacokinetics, pharmacodynamic assessments (changes in FOXP3 expression within tumor tissue –Stage 1b).

Exploratory pharmacodynamic endpoint: Changes in frequency of CCR8-expressing immune cell subsets in the periphery.

About CHS-114

CHS-114, a human, afucosylated anti-CCR8 monoclonal antibody, is designed to selectively target human CCR8 and preferentially deplete CCR8+ Tregs within the tumor microenvironment, while preserving effector T (Teff) cells in tumors or Tregs in normal tissue. In preclinical studies, CHS-114 induced antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP) to deplete tumoral CCR8+ Tregs. In addition, treatment with CHS-114 alone reduced tumor growth in murine models, and enhanced antitumor activity was observed in combination with anti-PD-1 treatment. CHS-114 is currently being evaluated in a Phase 1 clinical trial (NCT05635643) as a monotherapy and in combination with toripalimab in advanced solid tumors, including head and neck cancer. As reported in June 2023, early evidence of biological effect has been seen with CCR8+ Tregs depletion in blood following treatment with CHS-114, with no effect observed on non-CCR8+ Tregs.

About Coherus BioSciences 

Coherus is a commercial-stage biopharmaceutical company focused on researching, developing, and commercializing innovative therapies to treat cancer. Coherus is developing an innovative immuno-oncology pipeline expected to synergize with its proven commercial capabilities in oncology. 

Coherus’ immuno-oncology pipeline includes multiple antibody immunotherapy candidates focused on enhancing the innate and adaptive immune responses to enable a robust antitumor immunologic response and enhance outcomes for patients with cancer. Casdozokitug is a novel IL-27 antagonistic antibody currently being evaluated in two ongoing clinical studies: a Phase 1/2 study in advanced solid tumors and a Phase 2 study in hepatocellular carcinoma. CHS-114 is a highly selective, competitively positioned, cytolytic anti-CCR8 antibody currently in a Phase 1 study in patients with advanced solid tumors. CHS-1000 is a preclinical candidate targeting immune-suppressive mechanisms via the novel pathway ILT4, with a response from the FDA on Coherus’ IND filing expected in the second quarter of 2024.

Coherus markets LOQTORZI® (toripalimab-tpzi), a novel next-generation PD-1 inhibitor, UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta®, and YUSIMRY® (adalimumab-aqvh), a biosimilar of Humira®.

SOURCE: Coherus BioSciences