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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 22
- 主要终点
- Nature and frequency of dose-limiting toxicity(DLT)
研究概览
简要总结
A Phase 1 First-in-Human study of YL217 in Patients with Advanced Solid Tumors
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
- •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.
研究组 & 干预措施
Part 3: Dose-Expansion Part
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.
干预措施: YL217 (Drug)
Part 2: The backfill stage of 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).
干预措施: YL217 (Drug)
Part 1: Dose-Escalation Part
Participants will receive escalating doses of YL217 until doses for optimization are determined
干预措施: YL217 (Drug)
结局指标
主要结局
Nature and frequency of dose-limiting toxicity(DLT)
时间窗: 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
时间窗: Up to approximately 3 years
Nature and frequency of AEs with severity is aim to evaluate the safety of YL217.
objective response rate (ORR)
时间窗: 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).
次要结局
- Eastern Cooperative Oncology Group performance status (ECOG PS)(Up to approximately 3 years)
- To evaluate safety endpoint of peripheral oxygen saturation (SpO2)(Up to approximately 3 years)
- Characterize Pharmacokinetics(PK) parameter AUC(Up to approximately 3 years)
- Characterize Pharmacokinetics(PK) parameter Cmax(Up to approximately 3 years)
- Characterize Pharmacokinetics(PK) parameter Ctrough(Up to approximately 3 years)
- Characterize Pharmacokinetics(PK) parameter Tmax(Up to approximately 3 years)
- Characterize Pharmacokinetics(PK) parameter CL(Up to approximately 3 years)
- Characterize Pharmacokinetics(PK) parameter Vd(Up to approximately 3 years)
- Characterize Pharmacokinetics(PK) parameter t1/2(Up to approximately 3 years)
- Immunogenicity endpoint: Incidence of anti-YL217 antibody (ADAs).(Up to approximately 3 years)
- Disease control rate (DCR)(Up to approximately 3 years)
- Duration of response (DoR)(Up to approximately 3 years)
- Time to response (TTR)(Up to approximately 3 years)
- Depth of response (DpR)(Up to approximately 3 years)
- Progression-free survival (PFS)(Up to approximately 3 years)
- Overall survival (OS)(Up to approximately 3 years)