NCT06657144

Brief Summary

The main purpose of this study is to evaluate the safety and preliminary efficacy of CHS-114 in combination with toripalimab and/or other standard of care (SOC) compound(s) in participants with advanced or metastatic solid tumors.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
154

participants targeted

Target at P75+ for phase_1

Timeline
21mo left

Started Apr 2025

Typical duration for phase_1

Geographic Reach
2 countries

30 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress40%
Apr 2025Jan 2028

First Submitted

Initial submission to the registry

October 23, 2024

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 24, 2024

Completed
5 months until next milestone

Study Start

First participant enrolled

April 1, 2025

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2028

Last Updated

March 31, 2026

Status Verified

March 1, 2026

Enrollment Period

2.8 years

First QC Date

October 23, 2024

Last Update Submit

March 27, 2026

Conditions

Keywords

Solid TumorsAdvanced Solid TumorsMetastatic Solid TumorCancerOncologyTumorCCR8PD-1Gastric cancerGastro-esophageal-junction (GEJ) cancerEsophageal Adenocarcinoma (EAC)Esophageal Squamous Cell CarcinomaCisplatin5 Fluorouracil (5-FU)Colorectal Carcinoma (CRC)

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    From first dose of study drug until 90 days after the last dose of study drug (up to approximately 2.25 years)

Secondary Outcomes (9)

  • Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Investigator Assessment

    Up to approximately 2.25 years

  • Duration of Response (DOR) Per RECIST v1.1 Based on Investigator Assessment

    Up to approximately 2.25 years

  • Disease Control Rate (DCR) Per RECIST v1.1 Based on Investigator Assessment

    Up to approximately 2.25 years

  • Progression-free Survival (PFS) Per RECIST v1.1 Based on Investigator Assessment

    Up to approximately 2.25 years

  • Landmark PFS Rates

    Months 6, 9, and 12

  • +4 more secondary outcomes

Study Arms (7)

Cohort A - Arm A1: CHS-114 Dose A + Toripalimab

EXPERIMENTAL

Participants will be treated with dose A of CHS-114 administered as an intravenous (IV) infusion in combination with toripalimab every 3 weeks (Q3W).

Drug: CHS-114Drug: Toripalimab

Cohort A - Arm A2: CHS-114 Dose B + Toripalimab

EXPERIMENTAL

Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.

Drug: CHS-114Drug: Toripalimab

Cohort B - Arm B1: CHS-114 Dose A + Toripalimab

EXPERIMENTAL

Participants will be treated with dose A of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.

Drug: CHS-114Drug: Toripalimab

Cohort B - Arm B2: CHS-114 Dose B + Toripalimab

EXPERIMENTAL

Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.

Drug: CHS-114Drug: Toripalimab

Cohort C - Arm C: CHS-114 Dose B + Toripalimab + 5 fluorouracil (5 FU) + Cisplatin

EXPERIMENTAL

Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab, 5 FU, and cisplatin Q3W.

Drug: CHS-114Drug: ToripalimabDrug: 5 FluorouracilDrug: Cisplatin

Experimental: Cohort D - Arm D1 (Liver Mets): CHS-114 + Toripalimab

EXPERIMENTAL

Participants will be treated with CHS-114 administered as an IV infusion in combination with toripalimab Q3W.

Drug: CHS-114Drug: Toripalimab

Experimental: Cohort D - Arm D2 (Non-Liver Mets): CHS-114 + Toripalimab

EXPERIMENTAL

Participants will be treated with CHS-114 administered as an IV infusion in combination with toripalimab Q3W.

Drug: CHS-114Drug: Toripalimab

Interventions

Solution for infusion

Cohort A - Arm A1: CHS-114 Dose A + ToripalimabCohort A - Arm A2: CHS-114 Dose B + ToripalimabCohort B - Arm B1: CHS-114 Dose A + ToripalimabCohort B - Arm B2: CHS-114 Dose B + ToripalimabCohort C - Arm C: CHS-114 Dose B + Toripalimab + 5 fluorouracil (5 FU) + CisplatinExperimental: Cohort D - Arm D1 (Liver Mets): CHS-114 + ToripalimabExperimental: Cohort D - Arm D2 (Non-Liver Mets): CHS-114 + Toripalimab

Solution for infusion

Cohort A - Arm A1: CHS-114 Dose A + ToripalimabCohort A - Arm A2: CHS-114 Dose B + ToripalimabCohort B - Arm B1: CHS-114 Dose A + ToripalimabCohort B - Arm B2: CHS-114 Dose B + ToripalimabCohort C - Arm C: CHS-114 Dose B + Toripalimab + 5 fluorouracil (5 FU) + CisplatinExperimental: Cohort D - Arm D1 (Liver Mets): CHS-114 + ToripalimabExperimental: Cohort D - Arm D2 (Non-Liver Mets): CHS-114 + Toripalimab

Solution for infusion

Cohort C - Arm C: CHS-114 Dose B + Toripalimab + 5 fluorouracil (5 FU) + Cisplatin

Solution for infusion

Cohort C - Arm C: CHS-114 Dose B + Toripalimab + 5 fluorouracil (5 FU) + Cisplatin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • At least 1 measurable lesion based on RECIST v1.1 as determined by the Investigator.
  • Resolved acute effects of any prior therapy to baseline severity or Grade 1 in accordance with National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except for adverse events (AEs) not constituting a safety risk per Investigator judgement.
  • Histologically or cytologically documented unresectable, locally advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma that is human epidermal growth factor receptor 2 (HER2) - negative and microsatellite stable (MSS)/proficient mismatch repair (pMMR).
  • Progressed during or after first line systemic therapy that includes a platinum and fluoropyrimidine doublet with or without anti-programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1)-directed therapy (that is, in the second line setting).
  • Consent to provide tumor tissue samples (baseline and on-treatment) is required for enrollment.
  • Histologically or cytologically documented unresectable, locally advanced or metastatic ESCC.
  • Progressed during or after first line systemic therapy including a doublet of platinum and fluoropyrimidine or paclitaxel with or without anti-PD-1/PD-L1-directed therapy or anti-CTLA-4 and anti-PD-1/PD-L1-directed combination therapy.
  • Consent to provide results from prior PD-L1 IHC assay score by FDA-approved or equivalent PD-L1 IHC diagnostic tests.
  • Consent to provide archival tumor tissue sample (baseline) is required for enrolment.
  • Histologically or cytologically documented unresectable, locally advanced or metastatic ESCC.
  • Consent to provide baseline tumor tissue is required.
  • Consent to provide results from prior PD-L1 IHC assay score by FDA-approved or equivalent PD-L1 IHC diagnostic tests.
  • Calculated creatinine clearance ≥60 mL/min.
  • Histologically and/or cytologically documented unresectable advanced or metastatic colorectal adenocarcinoma. RAS, BRAF, and microsatellite instability/mismatch repair status for each participant must be documented, according to country level guidelines.
  • Participants who have no available therapies with a proven clinical benefit available in the participant's country per investigator. These therapies include the following: fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapy, anti-VEGF biological therapy (eg, bevacizumab, aflibercept, ramucirumab), an anti-EGFR therapy (eg, cetuximab, panitumumab) if RAS wildtype unless right-sided, either trifluridine/tipiracil, fruqintinib or regorafenib, and a BRAF inhibitor (ie, encorafenib) in BRAF V600E mutant).
  • +2 more criteria

You may not qualify if:

  • History of prior malignancy other than the cancer under study that is progressing or has required active treatment within the past 3 years.
  • Symptomatic or untreated central nervous system metastases, including leptomeningeal metastases, requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids.
  • Major surgery requiring general anesthesia within 28 days prior to the first dose of study treatment, still recovering from prior surgery, or with surgery scheduled during the study.
  • Prior exposure to anti-C-C motif chemokine receptor 8 (CCR8) antibody.
  • History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody (mAb) therapy or any excipient in the study treatment.
  • Active uncontrolled bacterial, fungal, or viral infection including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
  • Any condition that, in the opinion of the Investigator or Sponsor, would interfere with the interpretation of study results.
  • Received ≥ 2 prior systemic anticancer therapies for advanced or metastatic disease.
  • Participants at high risk for developing esophageal fistula by clinical assessment or imaging, such as prior history or associated symptoms of esophageal fistula or T4 classification assessed by endoscopic ultrasound (EUS).
  • Received ≥ 2 prior systemic anticancer therapies for advanced or metastatic disease.
  • Participants at high risk for developing esophageal fistula by clinical assessment or imaging, such as prior history or associated symptoms of esophageal fistula or T4 classification assessed by endoscopic ultrasound (EUS).
  • Received ≥ 1 prior systemic anticancer therapies for advanced or metastatic disease.
  • Participants who progressed during or within 6 months following the last dose of neoadjuvant, or perioperative therapy with curative intent.
  • Participants at high risk for developing esophageal fistula by clinical assessment or imaging, such as prior history or associated symptoms of esophageal fistula or T4 classification assessed by endoscopic ultrasound (EUS).
  • Known dihydropyrimidine dehydrogenase deficiency or thymidine synthase gene polymorphism predisposing the participant to 5-FU toxicity.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (30)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

University of Colorado - Aurora Cancer Center

Aurora, Colorado, 80045, United States

RECRUITING

Winship Cancer Center - Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Ochsner Health

New Orleans, Louisiana, 70121, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

RECRUITING

Comprehensive Cancer Center of Nevada

Las Vegas, Nevada, 89169, United States

RECRUITING

Christus St Vincent Regional Medical Center

Santa Fe, New Mexico, 87505, United States

RECRUITING

START New York

Lake Success, New York, 11042, United States

RECRUITING

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 11766, United States

RECRUITING

University of Pittsburg Medical Center _UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Prisma Health Cancer Institute

Greenville, South Carolina, 29605, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Texas Oncology - Central South

Austin, Texas, 78731, United States

RECRUITING

START San Antonio, LLC.

San Antonio, Texas, 78229, United States

RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

START Mountain Region, LLC.

West Valley City, Utah, 84119, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

RECRUITING

Changhua Christian Hospital

Chang-hua, Taiwan

RECRUITING

E-Da Cancer Hospital

Kaohsiung City, 824, Taiwan

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

RECRUITING

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

RECRUITING

China Medical University Hospital

Taichung, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, 704, Taiwan

RECRUITING

Chi Mei Hospital

Tainan, 736, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 112, Taiwan

RECRUITING

Mackay Memorial Hospital

Taipei, Taiwan

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.

MeSH Terms

Conditions

Neoplasm MetastasisNeoplasmsStomach NeoplasmsAdenocarcinoma Of EsophagusEsophageal Squamous Cell CarcinomaColorectal Neoplasms

Interventions

toripalimabFluorouracilCisplatin

Condition Hierarchy (Ancestors)

Neoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and SymptomsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesGastrointestinal DiseasesStomach DiseasesCarcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasms, Squamous CellEsophageal NeoplasmsHead and Neck NeoplasmsEsophageal DiseasesIntestinal NeoplasmsColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

UracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum Compounds

Central Study Contacts

Clinical Operations Team

CONTACT

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

October 23, 2024

First Posted

October 24, 2024

Study Start

April 1, 2025

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

January 1, 2028

Last Updated

March 31, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Locations