A Phase I/II Trial of EMB-02, a Bi-specific Antibody Against PD-1 and LAG-3, in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 47
- 试验地点
- 15
- 主要终点
- Dose intensity
研究概览
简要总结
The primary purpose of this study is to identify the recommended Phase 2 dose(s) (RP2Ds) and schedule assessed to be safe for EMB-02 and to characterize the safety and tolerability of EMB-02 at the RP2Ds. Pharmacokinetics (PK), immunogenicity, and the anti-tumor activity of EMB-02 will also be assessed.
详细描述
This is a Phase I/II, multi-center, open label, multiple-dose, first in human study, designed to assess safety and tolerability, and to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dos(s)e (RP2D[s]) for EMB-02 in patients with advanced solid tumors. Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.
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
- •Willing and able to provide written informed consent.
- •Phase I: Patients with histologically or cytologically confirmed locally advanced/metastatic solid tumors and have failed (progressed on, or are intolerant of) standard therapies. Moreover, the disease should be measurable or evaluable per RECIST v1.1
- •Phase II Cohort A: Patients with histologically or cytologically confirmed locally advanced/metastatic melanoma, excluding uveal melanoma. > 1 prior therapy, including prior treatment with PD-1/L1(mandatory) and/or CTLA-4 inhibitors(optional). And the disease is measurable or evaluable per RECIST v1.1
- •Archival tumor samples available for retrospective analysis or biopsy will be taken.
- •ECOG performance status 0 or 1 for phase I, and ≤2 for phase II; life expectancy > 3 Months
- •Adequate organ function to participate in the trial.
- •Recovery from adverse events (AEs) related to prior anticancer therapy.
- •Highly effective contraception
排除标准
- •Patients who have active autoimmune disease or history of autoimmune disease
- •History of severe irAE.
- •History of severe allergic reactions
- •Use of systemic corticosteroids.
- •Symptomatic central nervous system metastases.
- •Patients with cardiac dysfunction
- •Uncontrolled diabetes mellitus with hemoglobin A1c > 8% (via medical history)
- •Prior treatment with a LAG-3 inhibitor
- •Anticancer therapy or radiation < 5 half-lives or 4 weeks (whichever is shorter) prior to study treatment;
- •Prior organ or stem cell/bone marrow transplant.
- •Concurrent malignancy < 5 years prior to entry.
- •Patients with active infections.
- •Major surgery < 4 weeks or minor surgery < 2 weeks prior to study treatment
- •Live virus vaccines < 30 days prior to screening
- •Pregnant or breast-feeding females
- •Any investigational agents or study drugs from a previous clinical study within 30 days of the first dose of study treatment
- •Any other serious underlying medical conditions
- •Abuse on alcohol, cannabis- derived products or other drugs
结局指标
主要结局
Dose intensity
时间窗: Screening up to follow-up (30 days after the last dose)
Actual amount of drug taken by patients divided by the planned amount.
Incidence of dose interruptions
时间窗: Screening up to follow-up (30 days after the last dose)
Incidence of dose interruptions of EMB-02 during treatment as a measure of tolerability.
Incidence and severity of adverse events as assessed by CTCAE V5.0
时间窗: Screening up to follow-up (30 days after the last dose)
Incidence and severity of AE.
Incidence of serious adverse events (SAE)
时间窗: Screening up to follow-up (30 days after the last dose)
Incidence of SAE.
The incidence of DLTs during the first cycle of treatment.
时间窗: First infusion to the end of Cycle 1 (each cycle is 28 days)
The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and are specifically defined in study protocol.
Antitumor activity(Objective Response Rate (ORR)
时间窗: From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months
Measured by RECIST 1.1, only applicable in Phase II part
次要结局
- Maximum serum concentration (Cmax) of EMB-02(Through treatment until EOT visit, expected average 6 months)
- Average concentration over a dosing interval (Css, avg)of EMB-02.(Through treatment until EOT visit, expected average 6 months)
- Systemic clearance (CL) of EMB-02(Through treatment until EOT visit, expected average 6 months)
- Area under the serum concentration-time curve (AUC) of EMB-02(Through treatment until EOT visit, expected average 6 months)
- Trough concentration (Ctrough) of EMB-02(Through treatment until EOT visit, expected average 6 months)
- Progression free survival (PFS) of EMB-02 as assessed by RECIST 1.1(From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months)
- Terminal half-life (T1/2) of EMB-02(Through treatment until EOT visit, expected average 6 months.)
- Steady state volume of distribution (Vss) of EMB-02(Through treatment until EOT visit, expected average 6 months)
- Duration of response of EMB-02 as assessed by RECIST 1.1(From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months)
- Incidence and titer of anti-drug antibodies stimulated by EMB-02(Up to End of Treatment Follow Up Period (30 days after the last dose))