A Phase 1 First-in-Human study of YL217 in Patients with Advanced Solid Tumors
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
Mayo Clinic Arizona
Phoenix, Arizona, United States
Nature and frequency of dose-limiting toxicity(DLT)
The purpose of DLT is to find maximum tolerated dose (MTD).
Time frame: Up to approximately 3 years
Nature and frequency of adverse events (AEs) with severity
Nature and frequency of AEs with severity is aim to evaluate the safety of YL217.
Time frame: Up to approximately 3 years
objective response rate (ORR)
ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR).
Time frame: Up to approximately 3 years
Eastern Cooperative Oncology Group performance status (ECOG PS)
Deterioration of Eastern Cooperative Oncology Group performance status (ECOG PS)
Time frame: Up to approximately 3 years
To evaluate safety endpoint of peripheral oxygen saturation (SpO2)
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter AUC
The area under curve: AUC is the total amount of YL217 in bloodstream after drug administration.
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Cmax
Maximum concentration:The highest measured concentration of YL217 in the bloodstream.
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Ctrough
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UCLA Hematology/Oncology - Santa Monica
Santa Monica, California, United States
RECRUITINGYale Cancer Center
New Haven, Connecticut, United States
RECRUITINGThe University of Kansas Cancer Center (KUCC)
Kansas City, Kansas, United States
RECRUITINGUniversity of Maryland Medical Center-Greenebaum Cancer Ctr - Medical Oncology
Baltimore, Maryland, United States
NOT_YET_RECRUITINGKarmanos Cancer Institute
Detroit, Michigan, United States
RECRUITINGColumbia University Irving Medical Center
New York, New York, United States
RECRUITINGDuke University Medical Center (DUMC)
Durham, North Carolina, United States
RECRUITINGUniversity of Cincinnati Medical Center
Cincinnati, Ohio, United States
RECRUITINGCleveland Clinic Taussig Cancer Institute
Cleveland, Ohio, United States
RECRUITING...and 9 more locations
Trough concentration
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Tmax
Time to maximum observed concentration
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter CL
Clearance: defined as the amount of drug removed from the bloodstream by the body per unit of time.
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Vd
volume of distribution
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter t1/2
Half-life time:defined as the time it takes for the concentration of the drug in plasma or serum to be reduced by 50%.
Time frame: Up to approximately 3 years
Immunogenicity endpoint: Incidence of anti-YL217 antibody (ADAs).
The presence of ADAs in patients treated with YL217 will be assessed to evaluate immunogenicity.
Time frame: Up to approximately 3 years
Disease control rate (DCR)
DCR: defined as the proportion of patients who achieved a best overall response of complete response (CR), partial response (PR) or stable disease (SD).
Time frame: Up to approximately 3 years
Duration of response (DoR)
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 frame: Up to approximately 3 years
Time to response (TTR)
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).
Time frame: Up to approximately 3 years
Depth of response (DpR)
DpR: defined as the proportion of target lesion shrinkage from baseline to maximum tumor size.
Time frame: Up to approximately 3 years
Progression-free survival (PFS)
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.
Time frame: Up to approximately 3 years
Overall survival (OS)
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.
Time frame: Up to approximately 3 years