A First-in-human, Phase I Trial of EMB-09, a Bispecific Antibody Targeting PD-L1 and OX-40 in Patients With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Incidence and severity of adverse events as assessed by CTCAE V5.0
研究概览
简要总结
This study is to evaluate the safety and tolerability of EMB-09 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Pharmacokinetics (PK), immunogenicity, and the anti-multiple myeloma activity of EMB-09 will also be assessed.
详细描述
This is a phase I, 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 dose for EMB-09 in patient with advanced or metastatic 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 signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures.
- •Phase I subjects:
- •Patients with histologically or cytologically confirmed locally advanced/metastatic solid tumors including but not limited to melanoma, non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), head and neck squamous cell carcinoma (HNSCC), nasopharyngeal cancer (NPC), hepatocellular carcinoma (HCC), gastric cancer (GC), endometrium cancer (EC), ovarian cancer (OC), renal cell carcinoma (RCC) and small cell lung cancer (SCLC), colorectal cancer (CRC).
- •Patients who have failed (progressed on, or are intolerant of) standard therapies or no available standard treatment
- •Measurable or evaluable disease per RECIST v1.
- •Patients must provide archival tumor, or a fresh tumor biopsy will be required if archival tumor sample is not available. Archival tumor sample must be taken <2 years prior to screening, otherwise a fresh tumor biopsy at screening is required.
- •ECOG performance status 0 or 1; 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 TNFRSF agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR), CD
- •Anticancer therapy or radiation < 5 half-lives or 4 weeks (whichever is shorter) prior to study treatment;
- •Current or history of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia.
- •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 of alcohol, cannabis-derived products, or other drugs.
结局指标
主要结局
Incidence and severity of adverse events as assessed by CTCAE V5.0
时间窗: Screening up to 30 days after the last dose.
Incidence and severity of AE.
Dose intensity.
时间窗: Screening up to 30 days after the last dose.
Actual amount of drug taken by patients divided by the planned amount.
Incidence of serious adverse events. (SAE)
时间窗: Screening up to 30 days after the last dose, or beyond 30 days if SAE is confirmed to be treatment related.
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 are based on drug related adverse events and are specifically defined in study protocol.
Incidence of dose interruptions.
时间窗: Screening up to 30 days after the las dose.
Incidence of dose interruptions of EMB-09 during treatment as a measure of tolerability.
次要结局
- Area under the serum concentration-time curve (AUC) of EMB-09(Through treatment until EOT visit, expected average 6 months)
- Progression free survival (PFS) of EMB-09 as assessed by RECIST 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)
- Overall response rate(From the date of dosing until the date of first documented progression or date of death from any cause, whichever case first, expected average 6 months.)
- Steady state volume of distribution (Vss) of EMB-09(Through treatment until EOT visit, expected average 6 months)
- Incidence and titer of anti-drug antibodies stimulated by EMB-09(Up to End of Treatment Follow Up Period (30 days after the last dose)
- Trough concentration (Ctrough) of EMB-09(Through treatment until EOT visit, expected average 6 months)
- Average concentration over a dosing interval (Css, avg)of EMB-09.(Through treatment until EOT visit, expected average 6 months)
- Maximum serum concentration (Cmax) of EMB-09(Through treatment until EOT visit, expected average 6 months)
- Terminal half-life (T1/2) of EMB-09(Through treatment until EOT visit, expected average 6 months)
- Systemic clearance (CL) of EMB-09(Through treatment until EOT visit, expected average 6 months)