A Phase 1, First-in-Human, Multicenter, Open-label, Dose-escalation Study of IPH5201 as Monotherapy or in Combination With Durvalumab ± Oleclumab in Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 9
- 主要终点
- Incidence of adverse events as a measure of safety
研究概览
简要总结
The purpose of this study is to assess the safety and tolerability and to determine the dose of IPH5201 that can be used as monotherapy or in combination with durvalumab +/- oleclumab in subjects with advanced solid tumors.
详细描述
Study D6770C00001 is a Phase 1, first-in-human, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, antitumor activity, pharmacokinetics, and immunogenicity of IPH5201 in adult subjects with advanced solid tumors, when administered as monotherapy or in combination with durvalumab ± oleclumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 101 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult subjects; age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Subjects diagnosed with advanced solid tumors.
- •For Part 1 and Part 2 (IPH5201 in monotherapy or combined with durvalumab):Subjects must be refractory to standard therapy or for which no standard therapy exists.
- •For Part 3 (IPH5201 combined with durvalumab and oleclumab): Subjects must have received and radiologically progressed on 1 prior line of systemic therapy for metastatic pancreatic ductal adenocarcinoma.
- •Subjects must have at least 1 measurable lesion according to RECIST v1.
- •Subjects must provide tumor specimens .
排除标准
- •Receipt of any conventional or investigational anticancer therapy (anti-CTLA-4, anti-PD-1, anti-PD-L1 antibodies) within 21 days of the planned first dose.
- •Receipt of agents targeting CD73, CD39, or adenosine receptors.
- •Concurrent enrollment in another therapeutic clinical study.
- •Any toxicity (excluding alopecia) from prior standard therapy that has not been completely resolved to baseline at the time of consent.
- •No toxicity leading to permanent discontinuation of prior IO therapy
- •Subjects must not have required the use of additional immunosuppression other than corticosteroids
- •Active or prior documented autoimmune or inflammatory disorders within the past 5 years
- •Cardiac and vascular criteria:
- •Presence of myocardial infarction or unstable angina , or stroke, within 6 months.
- •Congestive heart failure, serious cardiac arrhythmia requiring medication, or uncontrolled hypertension
- •History of severe hypertension
- •History of any grade of blood clot within 6 months
- •Active infection, including tuberculosis; hepatitis B virus (HBV); hepatitis C virus (HCV); or human immunodeficiency virus (HIV)
- •Uncontrolled illness including certain lung diseases, uncontrolled diabetes, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study.
- •Other invasive malignancy within 2 years.
- •Major surgery within 28 days prior to first dose
- •Female subjects who are pregnant or breast feeding
结局指标
主要结局
Incidence of adverse events as a measure of safety
时间窗: From time of informed consent through treatment period and including the follow-up 12 weeks after last dose of investigational product, approximately 7 months
The primary endpoint is safety as assessed by the presence of adverse events (AEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs).
Incidence of clinically significant electrocardiogram (ECG) abnormalities as a measure of safety
时间窗: From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximatley 7 months
12 lead ECGs will be measured to identify clinical significant abnormalities including ECGs that demonstrate a QTcF value \>500ms, 2 additional 12-lead ECGs should be obtained over a 30 minute time period to confirm prolongation based on the average QTcF value
Incidence of clinically significant laboratory values as a measure of safety
时间窗: From time of informed consent through 12 weeks after the last dose of investigational product, approximately 7 months
Number of subjects with clinically significant laboratory values from baseline including blood counts, liver, kidney and pancreas tests, electrolytes, and blood clotting.
次要结局
- OR (Objective Response; Response evaluation criteria in solid tumors [RECIST] v1.1)(From time of consent until date of first documented disease progression (approximately 4 months))
- Maximum serum concentration (Cmax) of IPH5201(From start of treatment through Cycle 6 (21 day cycle, approximately 5 months))
- Half-life of IPH5201(From start of treatment through Cycle 6 (21 day cycle, approximately 5 months))
- DC (Disease Control; RECIST 1.1)(From time of consent until date of first documented disease progression (approximately 4 months))
- Area under the curve (AUC) of IPH5201(From start of treatment through Cycle 6 (21 day cycle, approximately 5 months))
- Serum trough concentrations (oleclumab)(From start of treatment through Cycle 6 (21 day cycle, approximately 5 months))
- Incidence of antidrug antibodies (IPH5201)(From start of treatment until 90 days after end of treatment (approximately 7 months))
- Incidence of antidrug antibodies (oleclumab)(From start of treatment until 90 days after end of treatment (approximately 7 months))
- Serum trough concentrations (durvalumab)(From start of treatment through Cycle 6 (21 day cycle, approximately 5 months))
- Incidence of antidrug antibodies (durvalumab)(From start of treatment until 90 days after end of treatment (approximately 7 months))