Study of CHS-114 in Participants With Advanced Solid Tumors

NCT05635643 | Recruiting Phase 1 FDA Drug

• 1 other identifier: SRF114-101
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 16

Brief Summary

This is a Phase 1, open-label, first-in-human, dose-escalation and expansion study of CHS-114, a monoclonal antibody that targets CCR8, as a monotherapy in patients with solid tumors.

Conditions

Advanced Solid Tumor; Head and Neck Squamous Cell Carcinoma

Keywords

metastatic solid tumors; advanced solid tumors; Phase 1; SRF114; CCR8; safety; efficacy; immunotherapy; cancer; immuno-oncology; CHS-114

Outcome Measures

Primary Outcomes (3)

• [Arms 1a, 1b, and 2] Rate of Dose Limiting Toxicity (DLT)

  Evaluation of rate of DLT of CHS-114 as a monotherapy, or in combination with toripalimab

  Assessed during first 21 days of treatment

• [Arm 2] Summary of adverse events (AEs) based on treatment emergent AEs (TEAEs), anti-drug antibodies (ADA), and laboratory values.

  Safety and tolerability of CHS-114 in combination with toripalimab,

  Up to 24 months

• [Arm 3] Safety and tolerability of CHS-114 in combination with toripalimab will be assessed by summarizing AEs and will be based on TEAEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 or higher.

  Safety and tolerability of CHS-114 in combination with toripalimab

  Up to 24 months

Secondary Outcomes (8)

• [Arms 1a and 1b] Summary of AEs based on TEAEs.

  Up to 24 months

• [Arms 1a and 1b] ADAs to CHS-114

  Up to 24 months

• [Arms 1a, 1b, 2, and 3] PK of CHS-114

  Up to 24 months

• [Arms 1a, 1b, 2, and 3] Confirmed objective response rate (ORR)

  Up to 24 months

• [Arms 1a, 1b, 2, and 3] Duration of response (DoR)

  Up to 24 months

Study Arms (4)

Arm 1a: CHS-114 Dose Escalation

EXPERIMENTAL

Arm 1 monotherapy dose escalation portion of the study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of CHS-114 as monotherapy in up to 25 participants with advanced solid tumors, to determine the recommended dose for expansion (RDE).

Drug: CHS-114

Arm 1b: CHS-114 Dose Expansion

EXPERIMENTAL

Arm 1b monotherapy expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 monotherapy at 2 dose levels (potential recommended dose for expansion RDE in up to 5 participants in each dose level with Head and Neck Squamous Cell Carcinoma (HNSCC).

Drug: CHS-114

Arm 2: CHS-114 + toripalimab Dose Escalation

EXPERIMENTAL

Arm 2 dose escalation will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 in combination with toripalimab at 2 RDE levels in up to 6 participants in each dose level with HNSCC.

Drug: CHS-114; Drug: toripalimab

Arm 3: CHS-114 + toripalimab Dose Expansion

EXPERIMENTAL

Arm 3 dose expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-114 in combination with toripalimab at 2 RDE levels in up to 20 participants in each dose level with HNSCC.

Drug: CHS-114; Drug: toripalimab

Interventions

CHS-114 DRUG

CHS-114

Arm 1a: CHS-114 Dose Escalation; Arm 1b: CHS-114 Dose Expansion; Arm 2: CHS-114 + toripalimab Dose Escalation; Arm 3: CHS-114 + toripalimab Dose Expansion

toripalimab DRUG

toripalimab-tpzi

Also known as: Loqtorzi

Arm 2: CHS-114 + toripalimab Dose Escalation; Arm 3: CHS-114 + toripalimab Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be ≥ 18 years of age.
• For Arm 1a only, locally advanced or metastatic (Stage IV) solid tumor that has progressed during or after standard therapy and for whom no available therapies are appropriate (based on the judgment of the Investigator).
• At least 1 measurable lesion per RECIST 1.1.
• Lesions previously treated with radiation or other forms of locoregional therapy must show radiographic evidence of disease progression to be used as a target lesion.
• For Arms 1a, 1b, and 2 only, washout period from the last dose of previous anticancer therapy (chemotherapy, biologic, or other investigational agent) to the initiation of study drug must be \> 5 times the half-life of the agent or \> 21 days (whichever is shorter).
• Resolution of non-immune-related AEs secondary to prior anticancer therapy (excluding alopecia and peripheral neuropathy) to ≤ Grade 1 per NCI-CTCAE version 5.0 or higher, and complete resolution of immune-related AEs secondary to prior checkpoint inhibitor therapy.
• Serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula.
• Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN if elevated because of liver metastases or documented Gilbert's syndrome).
• Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) \< 2.5 × ULN or \< 5 × ULN for patients with known liver metastases.
• Adequate hematologic function, defined as absolute neutrophil count ≥ 1.0 × 10\^9/L, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 75 × 10\^9/L.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Ejection fraction ≥ 50%, as measured by echocardiogram, multigated acquisition scan, nuclear stress test, or equivalent modality.
• Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study treatment period, including 90 days after the last dose of CHS-114, 4 months after the last dose of toripalimab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception. Azoospermic male patients and women of childbearing potential who are continuously not heterosexually active are exempt from contraceptive requirements.
• Histologically or cytologically confirmed advanced or metastatic HNSCC that has progressed during or after a platinum-based chemotherapy and/or a programmed cell death receptor (PD)-1 or PD ligand 1 (PD-L1) targeting agent (separately or in combination therapy).
• Metastatic or locoregionally recurrent HNSCC malignancy that is incurable by surgery or radiotherapy.

You may not qualify if:

• Previously received an anti-CCR8 antibody or anti-CCR8 targeted therapy.
• History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs.
• Major surgery within 4 weeks prior to Screening.
• Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes, symptomatic fistula) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study.
• Received \> 4 prior systemic regimens for advanced/metastatic disease.
• Nasopharyngeal carcinoma or nasal cavity malignancies other than HNSCC (eg, adenocarcinoma and variants, neuroendocrine tumors, mucosal melanoma).
• Receiving chronic anti-coagulation therapy (eg, warfarin, enoxaparin) that cannot be safely discontinued temporarily for the required biopsies (only for patients who provide tumor biopsies).
• Received ≥ 2 prior systemic regimens for advanced/metastatic disease.

Sponsors & Collaborators

• Coherus Oncology, Inc.: lead

Study Sites (16)

Hoag Memorial Hospital

Newport Beach, California, 92663, United States

RECRUITING

FOMAT Medical Research

Oxnard, California, 93030, United States

RECRUITING

Stanford Cancer Center

Palo Alto, California, 94305, United States

RECRUITING

SCRI Lake Nona DDU (FL Cancer Specialists)

Orlando, Florida, 32827, United States

RECRUITING

Emory Winship Cancer Institute

Atlanta, Georgia, 30308, United States

RECRUITING

Hope & Healing Cancer Services

Hinsdale, Illinois, 60521, United States

RECRUITING

University of Louisville

Louisville, Kentucky, 40202, United States

RECRUITING

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48104, United States

RECRUITING

Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center

Detroit, Michigan, 48201, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45219, United States

RECRUITING

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37203, United States

RECRUITING

START- San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

START Mountain

West Valley City, Utah, 84119, United States

RECRUITING

University of Washington/Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (1)

• Wang X, Kapoor VN, Chin DJ, Klakamp SL, Baruffaldi F, Mohan JF, Haines R, Dulak A, Panduro M, Ren Y, Masia R, Hill JA, LaVallee TM, Rajasekaran N. CHS-114: an afucosylated anti-CCR8 monoclonal antibody that selectively depletes intratumoral Treg cells and induces antitumor immune responses. Mol Cancer Ther. 2025 Dec 22. doi: 10.1158/1535-7163.MCT-25-0367. Online ahead of print.

  PMID: 41423415 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Neoplasms

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Koho Izuka, MD

  Coherus BioSciences

  STUDY DIRECTOR

Central Study Contacts

Clinical Operations Team

CONTACT

800-794-5434; clinicaltrials@coherus.com

MD at Coherus, MD

CONTACT

1-800-794-5434

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2022
• First Posted: December 2, 2022
• Study Start: December 15, 2022
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)