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
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.
Arms & interventions
- DrugYL217
Patients will be treated with YL217 intravenous(IV)infusion.
- DrugYL217
Patients will be treated with YL217 intravenous(IV)infusion.
- DrugYL217
Patients will be treated with YL217 intravenous(IV)infusion.
Outcome measures
Primary
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
Secondary
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
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Cmax
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Ctrough
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Tmax
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter CL
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Vd
Time frame: Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter t1/2
Time frame: Up to approximately 3 years
Immunogenicity endpoint: Incidence of anti-YL217 antibody (ADAs).
Time frame: Up to approximately 3 years
Disease control rate (DCR)
Time frame: Up to approximately 3 years
Duration of response (DoR)
Time frame: Up to approximately 3 years
Time to response (TTR)
Time frame: Up to approximately 3 years
Depth of response (DpR)
Time frame: Up to approximately 3 years
Progression-free survival (PFS)
Time frame: Up to approximately 3 years
Overall survival (OS)
Time frame: Up to approximately 3 years
Eligibility criteria
Study locations (13)
Mayo Clinic Arizona
Phoenix, Arizona, 85054
UCLA Hematology/Oncology - Santa Monica
Santa Monica, California, 90404
Yale Cancer Center
New Haven, Connecticut, 06519
The University of Kansas Cancer Center (KUCC)
Kansas City, Kansas, 66205
University of Maryland Medical Center-Greenebaum Cancer Ctr - Medical Oncology
Baltimore, Maryland, 21201
Karmanos Cancer Institute
Detroit, Michigan, 48201
Columbia University Irving Medical Center
New York, New York, 10032
Duke University Medical Center (DUMC)
Durham, North Carolina, 27710
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio, 44195
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
UT Health San Antonio - Mays Cancer Center
San Antonio, Texas, 78229
University of Wisconsin Health - UW Carbone Cancer Center
Madison, Wisconsin, 53792