Advanced Solid Tumor
Conditions
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.
Interventions
DRUGYL217
Patients will receive specific dose of YL217 administered via intravenous(IV)infusion.
DRUGBevacizumab
Participants will receive bevacizumab administered via intravenous(IV) infusion,at 5mg/kg,Q2W.
Participants will receive 5 fluorouracil 2400mg/m2 and leucovorin 400mg/m2, administered via intravenous (IV) infusion, Q2W
Sponsors
MediLink Therapeutics (Suzhou) Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A Phase 1, Multicenter, Open-Label, First-in-Human Study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Pathologically confirmed diagnosis of an advanced solid tumor. For CRC cohorts: : Histologically or cytologically documented locally advanced unresectable or metastatic colorectal carcinoma that is not eligible for curative surgery and/or definitive chemoradiotherapy * 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, minor procedures (e.g., core needle biopsy, superficial biopsy) within 7 days before the first dose of study drug. * 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, fistula, GI obstruction within 6 months prior to the first dose of study drug administration or have active inflammatory bowel disease. * An active tuberculosis based on medical history. * Known human immunodeficiency virus (HIV) infection. * Active hepatitis C infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
Countries
China, United States
Contacts
CONTACTAngie Cao, MD
Outcome results
None listed