NCT02391727已完成1 期
A Phase 1, Multi-center, Open-Label Dose Escalation Study of SYN004 in Patients With Solid Tumors to Evaluate the Safety, Immunogenicity and Pharmacokinetics of SYN004 Following Administration of Eight Intravenous Doses
Synermore Biologics Co., Ltd.4 个研究点 分布在 1 个国家目标入组 10 人开始时间: 2015年5月1日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 4
- 主要终点
- Number of patients with adverse events
研究概览
简要总结
A first-in-human evaluation of SYN004, a monoclonal antibody that binds to the EGF receptor on cancer cells. Cetuximab, a marketed antibody, has been shown to be effective by inhibiting the growth of cancer cells thereby prolonging the life of patients who have received it. SYN004 is a closely related monoclonal antibody also binds to the EGF receptor in the same way. SYN004 might also inhibit cancer cells and prolong life but has been engineered to avoid some of the hypersensitivity reactions known to provoked by cetuximab.
详细描述
Study Design:
In this open-label, dose escalation study, subjects will receive a single IV loading dose of SYN004 on Day 1 of the first treatment week, followed by up to 7 fixed weekly doses of SYN004. Subjects will be assigned to loading and fixed doses by dose group.
Each dose group will comprise 3 subjects and may be expanded to 6 subjects. Subjects will enter dose groups in the order in which they are enrolled. There will be no intra-subject dose adjustments.
Only 1 subject in a cohort may receive the loading dose of SYN004 on any given day; at least 1 day must elapse before the next subject in the cohort receives the loading dose.
Study SYN004-001 Dose Matrix. Three initial subjects will be enrolled followed by an additional three if specified by protocol. Dose levels are specified below.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Note: No waivers of the study inclusion or
排除标准
- •will be granted.
- •Diagnosis of a solid tumor for which the accepted standard of care includesa licensed anti-EGFR therapy;
- •Tumor progression in patients with RAS wild type metastatic colorectal cancer irrespective of their exposure to licensed anti-EGFR therapy including anti-EGFR antibodies; OR Tumor progression in patients with metastatic colorectal cancer refractory to cetuximab or panitumumab or other anti-EGFR antibodies OR Tumor progression in patients with EGFR-mutated non-small cell lung cancer (NSCLC) who have refused therapy.
- •OR Tumor progression or recurrence in patients with squamous cell carcinoma of the head and neck irrespective of their exposure to licensed anti-EGFR therapy including anti-EGFR antibodies.
- •OR Patients with locally advanced or metastatic colorectal carcinoma who have
- •relapsed after standard of care treatment,
- •proved refractory to standard of care treatment
- •refused standard of care treatment
- •been found to be medically unsuitable for standard of care treatment
- •Completion of written informed consent procedure;
- •Male or female subjects over 17 years of age
- •Life expectancy of at least 3 months;
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2;
- •At least one measureable non-irradiated site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;
- •Adequate bone marrow function, with absolute neutrophil count (ANC) >1,500/mm3, platelet count >100,000/mm3, and hemoglobin > 10 g/mm3;
- •Adequate liver function, with bilirubin <1.5 x the upper limit of the normal range (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x the ULN;
- •Adequate renal function, with serum creatinine <1.5 mg/dL;
- •Adequate cardiac function, with left ventricular ejection fraction (LVEF) ≥50%, normal electrocardiogram, and absence of significant cardiac disease;
- •In women of childbearing potential (defined as women of reproductive capacity who are pre-menopausal or within 12 months of cessation of menses): negative serum pregnancy test and use of an acceptable non-hormonal method of contraception;
- •Ability to communicate with the investigator, and understand and comply with the requirements of the protocol;
- •Agrees to notify the investigator when deviating from the protocol requirements with regard to concomitant medications;
- •Agrees to stay in contact with the study site for the duration of the study and to provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study.
- •Exclusion Criteria:
- •Participation in a study of an investigational agent or use of an investigational device at the time of screening or within 4 weeks of enrollment;
- •Receipt of treatment with a monoclonal antibody (mAb) within 4 weeks of enrollment or not recovered from an adverse event (i.e., event is >Grade 1 or subject has not returned to baseline) due to treatment with a mAb administered >4 weeks before enrollment;
- •Receipt of chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrollment, or not recovered from an adverse event (i.e., event is >Grade 1 or subject has not returned to baseline) due to a previously-administered agent;
- •Major surgical procedure or significant traumatic injury within 4 weeks prior to screening;
- •Diagnosis of an additional malignancy that is progressing and requires treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone potentially curative therapy;
- •Active autoimmune disease requiring systemic treatment within the past 3 months, or a documented history of severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents (subjects with vitiligo or resolved childhood asthma/atopy are allowed);
- •Diagnosis of an immune deficiency;
- •Receipt of systemic steroids or any form of immunosuppressive therapy within 7 days prior to enrollment, with the following exceptions:
- •Stable doses of topical, ocular, intranasal or inhaled corticosteroids
- •Doses of systemic steroids that, in the opinion of the investigator, are pysiologic replacement doses
- •Systemic steroids as prophylactic treatment for subjects with allergy to contrast media
- •Non-absorbed intra-articular steroid injections
- •Systemic corticosteroids required for control of infusion reactions or AEs if doses have been tapered to <10 mg prednisone or equivalent for 2 weeks prior to the first study treatment
- •Evidence of interstitial lung disease or active, non-infectious pneumonitis;
- •Active infection requiring systemic therapy;
- •History of cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within 6 months prior to screening;
- •Active hepatitis B (i.e., hepatitis B surface antigen [HBsAg] positive) or hepatitis C (i.e., hepatitis C virus [HCV] ribonucleic acid [RNA; qualitative] is detected);
- •Serious non-healing wound, ulcer, or bone fracture;
- •Any severe or uncontrolled medical condition or other condition that could affect participation in the study;
- •Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the subject will comply with the protocol.
研究组 & 干预措施
SYN004
Other
open label study
干预措施: SYN004 (Biological)
结局指标
主要结局
Number of patients with adverse events
时间窗: 28 days of last SYN004 Administration
cutaneous toxicity, hypersensitivity
次要结局
- systemic clearance (CL)(84 days)
- volume of distribution in the terminal phase (Vdβ), and estimated steady-state volume of distribution (VSS)(84 days)
- maximum plasma concentration (Cmax)(84 days)
- elimination half-life (t½)(84 days)
- mean residence time (MRT)(84 days)
- elimination rate constant (λz)(84 days)
- area under the plasma concentration vs. time curve from 0 (initiation of infusion) to the time of the last detectable concentration (AUC0-t), AUC from time 0 extrapolated to infinity (AUC0-∞)(84 days)
- anti-cancer activity(84 days)
- time to Cmax (Tmax)(84 days)
研究者
研究点 (4)
Loading locations...
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