A Phase 1, Multicenter, Open-Label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of YL217 in Patients with Advanced Solid Tumors

Cancer Categories

Gastrointestinal (GI)

Karmanos Trial ID

2025-025

NCT ID

NCT06859762

Age Group

Adult

Scope

National

Phase

Phase I

Principal Investigator

Wasif
Saif, M.D., MBBS
Oncology - Medical View Profile

Objective:

Dose-Escalation Part (Part 1)

Primary Objectives:

To assess the safety and tolerability of YL217 in patients with advanced solid tumors
To determine the maximum tolerated dose (MTD) of YL217 in patients with advanced solid tumors

Secondary Objectives:

To characterize the pharmacokinetics (PK) of YL217 antibody-drug conjugate (YL217-ADC), YL217 total antibody (YL217-TAb), and unconjugated payload YL0010014, metabolite YL0010034 and, if applicable, other potential metabolite(s)
To evaluate immunogenicity as measured by the presence of anti-drug antibodies (ADAs) in patients treated with YL217
To document any preliminary efficacy of YL217 in patients with advanced solid tumors

Backfill Part (Part 2)

Primary Objectives:

To further evaluate the safety and tolerability of YL217 in patients with advanced solid tumors
To determine the recommended dose(s) for expansion (RDE(s)) of YL217 in patients with advanced solid tumors

Secondary Objectives:

To further evaluate the efficacy of YL217 in patients with advanced solid tumors
To characterize the PK of YL217-ADC, YL217-TAb, unconjugated payload YL0010014, metabolite YL0010034 and, if applicable, other potential metabolite(s)
To evaluate immunogenicity as measured by the presence of ADAs in patients treated with YL217

Dose-Expansion Part (Part 3)

Primary Objectives:

To further evaluate the efficacy of YL217 at the RDE(s) in patients with the selected advanced solid tumors such as colorectal adenocarcinoma, gastric, esophageal or gastroesophageal junction adenocarcinoma, and pancreatic adenocarcinoma
To determine the recommended phase 2 dose (RP2D) of YL217

Secondary Objectives:

To further evaluate the safety and tolerability of YL217 at the RDE(s) in patients with the selected advanced solid tumors
To characterize the PK of YL217-ADC, YL217-TAb, unconjugated payload YL0010014, metabolite YL0010034 and, if applicable, other potential metabolite(s)
To evaluate immunogenicity as measured by the presence of ADAs in patients treated with YL217

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Eligibility

Inclusion Criteria:

Informed of the study before the start of the study and voluntarily sign their name and date in the informed consent form (ICF)
Able and willing to comply with protocol visits and procedures
Aged ≥ 18 years
Eastern Cooperative Oncology Group performance status (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 a topoisomerase I inhibitor within protocol defined time before the first dose of study drug.
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.

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 1-800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 1-800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices