A Phase 1, Open-label, Multicenter, Dose Escalation Study of IBI363 (PD1-IL2m) in Subjects With Advanced Solid Malignancies or Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 4
- 主要终点
- Incidence of serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs)
研究概览
简要总结
This is a Phase 1, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, and DLTs to establish the maximum tolerated dose (MTD) or maximum administered dose (MAD), and the RP2D of sequential doses of IBI363 (study drug) in subjects with advanced, refractory solid malignancies or lymphomas.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Male or female subjects, ≥ 18 years
- •Subjects with a documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; subjects with documented lymphomas
- •Subjects with a malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor
- •Subjects who are refractory to or intolerant to existing therapy(ies) known to provide clinical benefit Note: Subjects may have received and failed prior therapy with a PD-1/PD-L1 inhibitor and be considered eligible for this trial.
- •Subjects with measurable or non-measurable disease according to RECIST v1.1 or standard criteria for lymphoma (Lugano 2014)
- •Subjects, both male and female, who are either not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug
- •Subjects with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol
排除标准
- •Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of study drug. Women of childbearing potential (WOCBP) or fertile men with WOCBP partner(s), not using and not willing to use a highly effective method of contraception.
- •Subjects with history of or known active seizure disorder, brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
- •Subjects with:
- •Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to first administration of study drug unless adequately treated and considered by the Investigator to be stable.
- •Active uncontrolled bleeding or a known bleeding diathesis.
研究组 & 干预措施
IBI363
Single arm
干预措施: IBI363 (Biological)
结局指标
主要结局
Incidence of serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs)
时间窗: up to 90 days after the last administration
An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is an important medical event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. A TEAE will be defined as any new AE that begins, or any pre-existing condition that worsens in severity, after at least 1 dose of study treatment has been administered. irAEs will be assessed.
Number of participants with abnormality in hematology parameters
时间窗: up to 90 days after the last administration
Blood samples will be collected to evaluate hemoglobin, mean corpuscular volume (MCV), white blood cell (WBC) count, platelets, 5-part differential white cell count, mean platelet volume and coagulation factors including international normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT)
Number of participants with abnormality in clinical chemistry parameters
时间窗: up to 90 days after the last administration
Blood samples will be collected to evaluate sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or blood urea nitrogen (BUN), bicarbonate, amylase, bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, lactate dehydrogenase and lipase.
Number of dose-limiting toxicity (DLT)
时间窗: 28 days during the first 4-week cycle
Incidence of dose-limiting toxicity (DLT) events
Number of participants with abnormality in routine urinalysis parameters
时间窗: up to 90 days after the last administration
Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, bilirubin, protein, glucose, ketones and urobilinogen.
Number of participants with abnormality in vital signs
时间窗: up to 90 days after the last administration
Blood pressure, pulse, respiratory rate, and temperature will be assessed.
Number of participants with abnormality in ECG parameters
时间窗: up to 90 days after the last administration
12-lead ECG will be obtained using an ECG machine. Participants will be in supine or a semi-recumbent position (about 30 degrees of elevation) and rested for approximately 2 minutes before ECGs are recorded.
次要结局
- progression-free survival (PFS)(Up to 2 years)
- Objective response rate (ORR)(Up to 2 years)
- Overall survival (OS)(through study completion, an average of 1 year)
- area under the curve (AUC)(Up to 2 years)
- half-life (t1/2) of IBI363(Up to 2 years)
- disease control rate (DCR)(Up to 2 years)
- survival rates (6-month and 1-year)(Up to 2 years)
- maximum concentration (Cmax)(Up to 2 years)
- clearance (CL)(Up to 2 years)
- time to response (TTR)(Up to 2 years)
- duration of response (DoR)(Up to 2 years)
- The incidence of ADA and NAb of IBI363(Up to 2 years)
- 6-month and 1-year PFS rate per RECIST v1.1 for subjects with solid tumors, and per Lugano 2014 for subjects with lymphomas(Up to 2 years)