A First-in-Human Study of YL217 in Patients With Advanced Solid Tumors
- Registration Number
- NCT06859762
- Lead Sponsor
- MediLink Therapeutics (Suzhou) Co., Ltd.
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 220
- 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.
- 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.
- Active hepatitis C infection.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part 2: The backfill stage of YL217 YL217 Patients will be enrolled at one or more dose levels that do not exceed the dose that is deemed safe and tolerable in dose escalation. Then several dose levels will be selected as the recommended dose for expansion (RDE). Part 1: Dose-Escalation Part YL217 Participants will receive escalating doses of YL217 until doses for optimization are determined Part 3: Dose-Expansion Part YL217 Upon completion of Part 1 and Part 2 with determination of MTD/RDE(s), the dose-expansion part will be conducted to further support the RP2D selection.
- Primary Outcome Measures
Name Time Method Nature and frequency of dose-limiting toxicity(DLT) Up to approximately 3 years The purpose of DLT is to find maximum tolerated dose (MTD).
Nature and frequency of adverse events (AEs) with severity Up to approximately 3 years Nature and frequency of AEs with severity is aim to evaluate the safety of YL217.
objective response rate (ORR) Up to approximately 3 years ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR).
- Secondary Outcome Measures
Name Time Method Characterize Pharmacokinetics(PK) parameter Tmax Up to approximately 3 years Time to maximum observed concentration
Characterize Pharmacokinetics(PK) parameter CL Up to approximately 3 years Clearance： defined as the amount of drug removed from the bloodstream by the body per unit of time.
Eastern Cooperative Oncology Group performance status (ECOG PS) Up to approximately 3 years Deterioration of Eastern Cooperative Oncology Group performance status (ECOG PS)
To evaluate safety endpoint of peripheral oxygen saturation (SpO2) Up to approximately 3 years Characterize Pharmacokinetics(PK) parameter AUC Up to approximately 3 years The area under curve: AUC is the total amount of YL217 in bloodstream after drug administration.
Characterize Pharmacokinetics(PK) parameter Cmax Up to approximately 3 years Maximum concentration：The highest measured concentration of YL217 in the bloodstream.
Characterize Pharmacokinetics(PK) parameter Ctrough Up to approximately 3 years Trough concentration
Characterize Pharmacokinetics(PK) parameter Vd Up to approximately 3 years volume of distribution
Characterize Pharmacokinetics(PK) parameter t1/2 Up to approximately 3 years Half-life time：defined as the time it takes for the concentration of the drug in plasma or serum to be reduced by 50%.
Immunogenicity endpoint: Incidence of anti-YL217 antibody (ADAs). Up to approximately 3 years The presence of ADAs in patients treated with YL217 will be assessed to evaluate immunogenicity.
Disease control rate (DCR) Up to approximately 3 years DCR: defined as the proportion of patients who achieved a best overall response of complete response (CR), partial response (PR) or stable disease (SD).
Duration of response (DoR) Up to approximately 3 years DoR: defined as the time interval from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of progressive disease (PD).
Time to response (TTR) Up to approximately 3 years TTR: defined as the time interval from the date of the first dose of study drug to the date of the first documentation of objective response (CR or PR).
Depth of response (DpR) Up to approximately 3 years DpR: defined as the proportion of target lesion shrinkage from baseline to maximum tumor size.
Progression-free survival (PFS) Up to approximately 3 years PFS: defined as the time interval from the date of the first dose of study drug to the date of first documentation of PD or death due to any cause, whichever occurs first.
Overall survival (OS) Up to approximately 3 years OS: defined as the time interval from the date of the first dose of study drug to the date of death due to any cause.
Related Research Topics
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Trial Locations
- Locations (13)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Cleveland Clinic Taussig Cancer Institute
🇺🇸Cleveland, Ohio, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
UT Health San Antonio - Mays Cancer Center
🇺🇸San Antonio, Texas, United States
University of Wisconsin Health - UW Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Peking Union Medical College Hospital
🇨🇳Beijing, Bejing, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, Tianjin, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
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