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NCT06859762PHASE1Recruiting

A First-in-Human Study of YL217 in Patients With Advanced Solid Tumors

MediLink Therapeutics (Suzhou) Co., Ltd.

Start Date

7/2/2025

Completion Date

7/1/2027

Summary

A Phase 1 First-in-Human study of YL217 in Patients with Advanced Solid Tumors

Detailed Description

YL217 is an antibody-drug conjugate (ADC) that targets CDH17 (Cadherin-17) protein and is being developed for the treatment of cancer. YL217 is comprised of three components: 1) YL217-mAb, a CDH17-targeting recombinant humanized immunoglobulin G1 (IgG1) monoclonal antibody, 2) YL0010014, a topoisomerase I inhibitor, and 3) an enzymatically cleavable methylsulfonyl pyrimidine tripeptide drug linker. The in vivo anti-tumor efficacy of YL217 was evaluated in immune-deficient mice bearing human colorectal cancer, gastric cancer and patient derived colorectal cancer xenograft tumors. The results indicated that YL217 was well tolerated, and YL217 suppressed growth of established human tumors in a dose-dependent manner in cancer cells or patient derived xenograft models. Therefore, in order to meet the huge unmet medical needs in the field of gastrointestinal cancer treatment, it is planned to conduct the first human phase I clinical study of YL217 in patients with advanced solid tumors.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Informed of the study before the start of the study and voluntarily sign their name and date in the ICF * Able and willing to comply with protocol visits and procedures * Age≥ 18 years * ECOG PS of 0 or 1 * Tumor types as below: For Part 1 and Part 2: Pathologically confirmed diagnosis of an advanced solid tumor. For Part 3 (Histologically or cytologically confirmed diagnosis+ locally advanced unresectable or metastatic disease) * Adequate organ and bone marrow function. * Have at least 1 extracranial measurable tumor lesion. * Adequate archival formalin-fixed paraffin embedded (FFPE) tissue from prior biopsy. Exclusion Criteria: * Prior treatment with an agent targeting CDH17 * Prior discontinuation of a topoisomerase I inhibitor due to treatment-related toxicities. * Have received an ADC consisting of a topoisomerase I inhibitor. * Concurrent enrollment in another clinical study, unless it is an observational clinical study. * Inadequate washout period for prior anticancer treatment before the first dose of study drug * Undergone major surgery within 4 weeks before the first dose of study drug or expect major surgery during the study. * Received long term systemic steroids or other immunosuppressive therapy within 2 weeks before the first dose of study drug. * Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study. * Diagnosis or evidence of spinal cord compression or leptomeningeal carcinomatosis. * Uncontrolled or clinically significant cardiovascular and cerebrovascular diseases. * A history of non-infectious interstitial lung disease (ILD)/pneumonitis that requires steroids, current active ILD/pneumonitis. * Have clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses. * Uncontrolled third-space fluid that requires repeated drainage. * Digestive system disease that may cause bleeding, perforation, jaundice, gastrointestinal obstruction. * An active tuberculosis based on medical history. * Known human immunodeficiency virus (HIV) infection. * Active hepatitis C infection.

Interventions

DRUG

YL217

DRUG

YL217

DRUG

YL217

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Conditions

Advanced Solid Tumor

Locations

Mayo Clinic Arizona

Phoenix, Arizona 85054

United States

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California 90404

United States

Yale Cancer Center

New Haven, Connecticut 06519

United States

The University of Kansas Cancer Center (KUCC)

Kansas City, Kansas 66205

United States

University of Maryland Medical Center-Greenebaum Cancer Ctr - Medical Oncology

Baltimore, Maryland 21201

United States

Karmanos Cancer Institute

Detroit, Michigan 48201

United States

Columbia University Irving Medical Center

New York, New York 10032

United States

Duke University Medical Center (DUMC)

Durham, North Carolina 27710

United States

University of Cincinnati Medical Center

Cincinnati, Ohio 45219

United States

Cleveland Clinic Taussig Cancer Institute

Cleveland, Ohio 44195

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

UT Health San Antonio - Mays Cancer Center

San Antonio, Texas 78229

United States

University of Wisconsin Health - UW Carbone Cancer Center

Madison, Wisconsin 53792

United States

Peking Union Medical College Hospital

Beijing, Bejing 100730

China

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang 150081

China

Cancer Hospital of Shandong First Medical University

Jinan, Shandong 250117

China

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality 200025

China

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality 300060

China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang 310022

China