An Open-label, Multicenter, Multicohort Phase 1b/2 Clinical Trial of ES101 in Patients With Advanced Malignant Thoracic Tumors
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Phase 1b: Recommended Phase 2 Dose (RP2D) of of ES101
研究概览
简要总结
The purpose of this study is to evaluate the safety, RP2D and PK/pharmacodynamic profile of ES101 monotherapy in patients with advanced NSCLC and to further evaluate the antitumor efficacy of ES101 in advanced malignant thoracic tumors, including NSCLC and SCLC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Ability to understand and the willingness to sign a written informed consent form.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or
- •At least one measurable lesion is required (RECIST v1.1)
- •Phase 1b: Subjects with pathologically or cytologically confirmed recurrent or metastatic NSCLC without known EGFR mutation and ALK and ROS1 gene rearrangements.
- •Phase II: Subjects with pathologically or cytologically confirmed recurrent or metastatic malignant thoracic tumours who have received 1-2 lines of systemic anti-tumour therapy, including platinum regimens, and have failed, including at least 2 cycles of chemotherapy.
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.
- •Receipt of PD-L1 therapy within 24 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
- •Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Some exceptions as defined per protocol apply.
- •Subject has not recovered from all AEs of previous anticancer therapies to baseline or ≤ Grade 1 per CTCAE v5.0 before teh first dose of study drug. Certain exceptions as defined in 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.
- •Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications.
- •Systemic anti-infectious drug treatments within 4 weeks prior to the first dose of study drug.
- •Pregnant or nursing females.
研究组 & 干预措施
Cohort 1
ES101 is administered via intravenous infusion, 0.3mg/kg，once every 14 days, every 28 days as a treatment cycle.
干预措施: ES101 (Drug)
Cohort 2
ES101 is administered via intravenous infusion, 1mg/kg，once every 14 days, every 28 days as a treatment cycle.
干预措施: ES101 (Drug)
Cohort A1
ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.
干预措施: ES101 (Drug)
Cohort A2
ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.
干预措施: ES101 (Drug)
Cohort B
ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.
干预措施: ES101 (Drug)
Cohort C
ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.
干预措施: ES101 (Drug)
结局指标
主要结局
Phase 1b: Recommended Phase 2 Dose (RP2D) of of ES101
时间窗: 6 months
RP2D of ES101 will be determined.
Phase 1b: Frequency and severity of adverse events of ES101
时间窗: 1-2 years
Adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Phase 2: Objective response rate (ORR)
时间窗: 2-3 years
Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).
次要结局
- PD-L1 expression(2-4 years)
- Anti-tumor activity of ES101(2-4 years)
- PK profile of ES101(2-4 years)
- Immunogenicity of ES101(2-4 years)
- Pharmacodynamic markers(2-4 years)