NCT01646203已完成1 期
Phase 1 Study of Anti-TGFβRII Monoclonal Antibody IMC-TR1 (LY3022859) in Patients With Advanced Solid Tumors That Have Failed Standard Therapy or for Which No Standard is Available
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 4
- 主要终点
- Number of Participants With Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
A study to evaluate the safety and tolerability of anti-TGFβRII monoclonal antibody (IMC-TR1) in participants with advanced solid tumors, as well as gather evidence of anti-tumor activity.
详细描述
This is the first-in-human Phase 1 study of IMC-TR1.
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 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
- •Part A and Part B: Participants must be appropriate candidates for experimental therapy, with a solid tumor that has failed standard therapy or for which no standard therapy is available, and evidence of progressive disease
- •Part A only: Participants must have histological or cytological evidence of a solid tumor which is advanced and/or metastatic
- •Part B only: Participants who have failed first-line therapy/standard of care and have histological or cytological evidence of a cancer type for which evidence of activity was observed during Part A or for which preclinical evidence of potential activity has been observed
- •Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)
- •Part A only: Participants may have measurable or nonmeasurable disease
- •Part B: Participants must have measurable disease
- •Have adequate organ function including: Hematologic, Hepatic, Albumin, Coagulation and Renal function
- •Have a performance status of ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Have discontinued previous treatments for cancer and recovered from the acute effects of therapy
- •Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug
- •Females with child bearing potential must have had a negative serum pregnancy test and must not be breastfeeding
- •Have an estimated life expectancy that is > 3 months
排除标准
- •Have clinically significant cardiac disease, including:
- •Myocardial infarction within 6 months prior to study entry, unstable angina pectoris, congestive heart failure, or uncontrolled hypertension
- •Major electrocardiogram (ECG) abnormalities
- •Major abnormalities documented by echocardiography with Doppler
- •Have known predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress
- •Have Corrected QT Interval (QTc interval) of > 500 msec on screening ECG
- •Have other known serious pre-existing medical conditions
- •Have received prior investigational therapy targeting Transforming growth factor beta (TGFβ) or its receptors
- •Have a known sensitivity to monoclonal antibodies or other therapeutic proteins, to agents of similar biologic composition as IMC-TR1
- •Have a high risk of gastrointestinal bleeding, active inflammatory bowel disease, or chronic steroid use
- •Are currently using or has received a systemic thrombolytic agent within 28 days prior to enrollment
- •Are receiving:
- •full-dose warfarin
- •intravenous heparin or low-molecular-weight heparin
- •chronic daily treatment with aspirin at a dose greater than 325 mg per day or nonsteroidal anti-inflammatory medications known to inhibit platelet function
- •Have evidence of retinal disease or are a monocular participant
- •Have received a solid organ transplant, bone marrow transplant or stem cell transplant
- •Have symptomatic central nervous system (CNS) malignancy or untreated metastasis
- •Have acute or chronic leukemia
- •Have a known active fungal, bacterial, and/or viral infection including human immunodeficiency virus or viral hepatitis requiring treatment
- •Has a positive fecal occult blood test within 14 days prior to enrollment
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: First Dose Up to 6 Weeks
A DLT was defined as an AE occurring during Cycle 1(first 6 weeks of treatment) that was considered at least possibly related to study drug, was considered dose-dependent, and fulfilled a criteria selected (using the National Cancer Institute Common Terminology Criteria for Adverse Events,version 4.0 \[NCI-CTCAE v 4.0\] \[NCI 2009\]):Grade(Gr)≥3 nonhematological toxicity,Gr4 thrombocytopenia lasting at least 5 days and/or complicated with bleeding,Gr≥3 febrile neutropenia(ntr),Gr4 ntr of \>5 days' duration,increase(incr)of at least 1 gr from a preexisting Gr1 valvular insufficiency or any new Gr≥2 valvular toxicity,left ventricular(vtr) ejection fraction decrease of 10% in absolute value or 16% in relative value,incr in right vtr systolic pressure dysfunction from mild to moderate(mod) or from mod to severe,incr in left atrial or ventricular chamber size of ≥2 cm and ≥1cm respectively,any other life-threatening toxicity,significant morphologic on cardiac echocardiogram,any major ocular.
次要结局
- Number of Dose-Limiting Toxicities (DLTs)(First Dose through Cycle 1 (6 Weeks))
- Pharmacokinetics - Maximum Concentration (Cmax) of IMC-TR1(Cycle (C) 1 Day (D) 1: 1, 2, 4, 8 hours (h); C1 D2: 24 h; C1 D3: 48 h; C1 D5: 96 h; C1 D8: 168 h; C1 D15: 336 h; C2 D15: 1, 2, 4, 8 h; C2 D16: 24 h; C2 D17: 48 h; C2 D19: 96 h; C2 D22: 168 h, C2 D29: 336 h)
- Maximum Tolerated Dose (MTD) of IMC-TR1(First Dose through Cycle 1 (6 Weeks))
- Maximum Tolerated Dose (MTD) of IMC-TR1 (1.25 mg/kg LY3022859 ) for Participants Receiving a Weight-Based Dose(First Dose through Cycle 1 (6 Weeks))
- Immunogenicity - Development of Antibodies Against IMC-TR1(Cycle 1 - Day 1 and Day 29, Cycle 2 - Day 15, Cycle 3 and Each Consecutive Cycle - Day 1)
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) (Antitumor Activity of IMC-TR1 as Monotherapy, Assessed Via Tumor Measurement by Response Evaluation Criteria in Solid Tumors, Version 1.1)(First Dose to Measured Progressive Disease (Up To 21.3 Weeks))
- Pharmacokinetics (PK) - Area Under the Concentration-time Curve (AUC[0-tlast]) and AUCτ of IMC-TR1(Cycle (C) 1 Day (D) 1: 1, 2, 4, 8 hours (h); C1 D2: 24 h; C1 D3: 48 h; C1 D5: 96 h; C1 D8: 168 h; C1 D15: 336 h; C2 D15: 1, 2, 4, 8 h; C2 D16: 24 h; C2 D17: 48 h; C2 D19: 96 h; C2 D22: 168 h, C2 D29: 336 h)
- Pharmacokinetics - Minimum Concentration (Cmin) of IMC-TR1(Cycle 2 Day 1: Prior to fourth infusion 0 hour (h))
研究者
研究点 (4)
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