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NCT06657144PHASE1Recruiting

A Study of CHS-114 (Tagmokitug) in Combination With Toripalimab and/or Other Treatments in Participants With Advanced Solid Tumors

Coherus Oncology, Inc.

Start Date

4/1/2025

Completion Date

1/1/2028

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.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria: * 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. Cohort A (2L Gastric, Gastro-esophageal-junction \[GEJ\], Esophageal Adenocarcinoma \[EAC\]) Specific Inclusion Criteria: * 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. Cohort B (2L Esophageal Squamous Cell Carcinoma \[ESCC\]) - Specific Inclusion Criteria: * 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. Cohort C (1L Esophageal Squamous Cell Carcinoma \[ESCC\]) - Specific Inclusion Criteria: * 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. Cohort D, Arms D1 and D2 (4L+ Colorectal Carcinoma \[CRC\]) - Specific Inclusion Criteria: * 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). * Participants who received oxaliplatin in the adjuvant setting and developed metastatic disease during or within 6 months of completing adjuvant therapy are considered eligible without receiving oxalipatin-based therapy in the metastatic setting. * Consent to provide baseline tumor tissue sample is required for enrolment. Key Exclusion Criteria: * 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. Cohort A (2L Gastric, Gastro-esophageal-junction \[GEJ\], Esophageal Adenocarcinoma \[EAC\]) Specific Exclusion Criteria: * 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). Cohort B (2L Esophageal Squamous Cell Carcinoma \[ESCC\]) - Specific Exclusion Criteria: * 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). Cohort C (1L Esophageal Squamous Cell Carcinoma \[ESCC\]) - Specific Exclusion Criteria: * 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. * Known allergies to 5-FU or cisplatin. Note: Other protocol-specified inclusion/exclusion criteria apply.

Interventions

DRUG

CHS-114

DRUG

Toripalimab

DRUG

5 Fluorouracil

DRUG

Cisplatin

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Conditions

Metastatic Solid TumorAdvanced Solid Tumor

Locations

The University of Arizona Cancer Center

Tucson, Arizona 85724

United States

City of Hope

Duarte, California 91010

United States

University of Colorado - Aurora Cancer Center

Aurora, Colorado 80045

United States

Winship Cancer Center - Emory University

Atlanta, Georgia 30322

United States

Ochsner Health

New Orleans, Louisiana 70121

United States

Henry Ford Health System

Detroit, Michigan 48202

United States

Comprehensive Cancer Center of Nevada

Las Vegas, Nevada 89169

United States

Christus St Vincent Regional Medical Center

Santa Fe, New Mexico 87505

United States

START New York

Lake Success, New York 11042

United States

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

New York, New York 10065

United States

Icahn School of Medicine at Mount Sinai

New York, New York 11766

United States

University of Pittsburg Medical Center _UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania 15232

United States

Prisma Health Cancer Institute

Greenville, South Carolina 29605

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

Texas Oncology - Central South

Austin, Texas 78731

United States

START San Antonio, LLC.

San Antonio, Texas 78229

United States

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah 84112

United States

START Mountain Region, LLC.

West Valley City, Utah 84119

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031

United States

Virginia Oncology Associates

Norfolk, Virginia 23502

United States

Changhua Christian Hospital

Chang-hua,

Taiwan

E-Da Cancer Hospital

Kaohsiung City, 824

Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City,

Taiwan

Taichung Veterans General Hospital

Taichung, 40705

Taiwan

China Medical University Hospital

Taichung,

Taiwan

National Cheng Kung University Hospital

Tainan, 704

Taiwan

Chi Mei Hospital

Tainan, 736

Taiwan

National Taiwan University Hospital

Taipei, 10002

Taiwan

Taipei Veterans General Hospital

Taipei, 112

Taiwan

Mackay Memorial Hospital

Taipei,

Taiwan