An Open-label, Multicenter, Dose-escalation and Cohort Expansion Phase 1 Clinical Study of ES101 in Patients With Advanced Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- ES101
- 疾病 / 适应症
- Solid Tumors
- 发起方
- Elpiscience Biopharma, Ltd.
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of of ES101
- 状态
- 终止
- 最后更新
- 4年前
概览
简要总结
The purpose of this study is to evaluate the safety, tolerance and Dose-Limiting Toxicity (DLT) of recombinant humanized PD-L1/4-1BB bispecific antibody (ES101) in patients with advanced solid tumors.
详细描述
ES101 (INBRX-105; PDL1x4-1BB antibody) is a recombinant humanized bispecific IgG1 antibody targeting human PD-L1 and 4-1BB. This is an open-label, multicenter, dose-escalation and cohort expansion phase 1 clinical study to evaluate the safety and pharmacokinetic characteristics and preliminary anti-tumor activity of ES101 in patients with advanced malignant solid tumors whose disease has progressed despite standard therapy, or who has no further standard therapy, or who is unsuitable for available standard treatment options.
研究者
入排标准
入选标准
- •Males or females aged ≥ 18 years.
- •Subject has pathological or cytological diagnosed advanced malignant solid tumor, whose disease has progressed despite standard therapy, or who has no further standard therapy, or who is unsuitable for available standard treatment options
- •Part A: There is no mandatory requirement for PD-L1 expression status of subject's tumor tissue. Part B:Tumor tissue of subject should be PD-L1 positivity by immunohistochemistry (IHC).
- •Subjects in part A shall have at least one evaluable lesion, and subjects enrolled in part B shall have at least one measurable lesion (RECIST v1.1). Tumor lesions located in previously irradiated (or other local treated) areas will be considered measurable, provided that there has been clear imaging-based progression of the lesions since the time of radiation.
- •Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or
- •Estimated life expectancy, in the judgment of the investigator, of at least 12 weeks.
- •Male and female subjects of childbearing potential and their spouses must be willing to use feasible contraceptive methods considered effective by the investigator, from the time of signing informed consent and for the duration of study participation through 3 months, following the last dose of study drug. Postmenopausal women are considered to have no fertility potential only if menostasis lasts for at least 12 months.
- •Ability to understand and the willingness to sign a written informed consent form
排除标准
- •Prior exposure to 4-1BB agonists.
- •Receipt of any anticancer investigational product or any approved drug(s) or biological products (except hormone-replacement therapy, testosterone or oral contraceptives) within 4 weeks prior to the first dose of study drug. Previous exposure to oral fluorouracils or small molecular targeted drugs require a minimum washout period of 2 weeks or 5 half-lives prior to the first dose of study drug (whichever is longer). Previous exposure to mitomycin C or nitrosourea requires a minimum washout period of 6 weeks prior to the first dose of study drug.
- •Known allergies to CHO-produced antibodies, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to ES
- •Primary or metastatic brain or meningeal tumors.
- •Patients with other malignancies previously or currently shall be excluded in Part B.
- •Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Some exceptions as defined per protocol apply.
- •Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications. Certain exceptions as defined in protocol apply.
- •Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug. Certain exceptions as defined in protocol apply.
- •Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or immunosuppressive medications..
- •Subjects who received G-CSF, GM-CSF, Thrombopoietic drugs or EPO within 14 days prior to the first dose of the study drug.
研究组 & 干预措施
Part A dose escalation
ES101 will be escalated in patients with advanced solid tumors.
干预措施: ES101
Part B expansion
Subjects with solid tumors will be treated with single-agent ES101 at either specified dose levels or RP2D.
干预措施: ES101
结局指标
主要结局
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of of ES101
时间窗: Up to 2-3 years
The MTD and/or RP2D of ES101 will be determined.
Frequency of adverse events of ES101
时间窗: Up to 2-3 years
Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Severity of adverse events of ES101
时间窗: Up to 2-3 years
Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
次要结局
- Trough observed serum concentration (Ctrough) of ES101(Up to 2-3 years)
- Immunogenicity of ES101(Up to 2-3 years)
- Area under the serum concentration time curve (AUC) of ES101(Up to 2-3 years)
- Maximum observed serum concentration (Cmax) of ES101(Up to 2-3 years)
- Time to Cmax (Tmax) of ES101(Up to 2-3 years)
- Anti-tumor activity of ES101(Up to 2-3 years)