A Phase 1, Open-Label, Multiple-Ascending Dose Study of the Safety and Tolerability of CTX-10726 in Patients With Advanced Malignancies
概览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 3
- 主要终点
- Cohort 1: Evaluate the safety and tolerability of CTX-10726 by incidence of treatment-emergent adverse events (TEAEs) in escalating doses
概览
简要总结
This is a Phase 1, open-label, first-in-human study of CTX-10726 monotherapy in patients with metastatic or locally advanced malignancies. The study will be conducted in 2 Cohorts: Cohort 1 Dose Escalation and Cohort 2 Dose Expansion.
详细描述
This Phase 1, open-label, first-in-human study will evaluate the safety, tolerability, immunogenicity, and pharmacokinetics profile of CTX-10726 monotherapy. Preliminary anti-tumor activity of CTX-10726 will also be assessed. The study will be conducted in 2 cohorts: Dose escalation and Dose expansion. The Dose Escalation Cohort will utilize a 3+3 design to evaluate four dose levels (0.3-10.0mg/kg) of CTX-10726 given as an IV infusion once every 2 weeks. Patients in the Dose Expansion Cohort will receive CTX-10726 as an IV infusion at dose(s) based on data from the Dose Escalation Cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Age 18 years or older.
- •Patients must have a histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic disease that is relapsed/refractory to standard therapy or for which no effective standard therapy is available, including:
- •2a: Renal Cell Carcinoma (RCC)
- •Histologically confirmed diagnosis of renal cell carcinoma (with clear cell component) with advanced or metastatic disease that is not amenable to cure by surgery or other means.
- •Patients who have progressed after a minimum of 2 doses of a programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PDL1) treatment.
- •Patients must have received at least one regimen including a tyrosine kinase inhibitor (TKI).
- •Patients who received immunomodulatory drugs (thymosin, interferon, interleukin, etc.) within 2 weeks before the first dose or received major surgical treatment within 3 weeks before the first dose are not eligible.
- •2b: Hepatocellular Carcinoma (HCC)
- •Patients who have progressed after a minimum of 2 doses of a PD-1/PDL1 treatment.
- •Patient must have received one of the following regimens: ipilimumab+nivolumab, tremelimumab+durvalumab or atezolizumab+bevacizumab.
排除标准
- •Developed clinically significant adverse reaction to PD-1 or PD-L1 therapy, including immune related adverse reactions, which led to discontinuation of treatment.
- •Prior organ transplantation.
- •History of arterial or venous thrombosis or stroke or transient ischemic attack within 6 months prior to the first dose.
- •History of other neoplasms within 3 years prior to screening, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical cancer in situ that has undergone successful surgery.
- •Known, symptomatic central nervous system (CNS) and brain metastasis.
- •A pleural, abdominal or pericardial effusion that is clinically symptomatic or requires repeated management (puncture or drainage, etc).
- •Imaging at screening that shows the tumor surrounds important blood vessels or had obvious necrosis and voids, and the investigators deems that it might cause bleeding risk.
- •The presence of severe, unhealed or open wounds, active ulcers, or untreated fractures at the time of screening.
- •A history of significant bleeding tendency or severe coagulopathy.
- •Current therapeutic dose of anticoagulant or thrombolytic medication within 14 days of the first dose. Note: prophylactic use of low molecular heparin is allowed.
研究组 & 干预措施
Dose Escalation Cohort 1
Escalating doses of CTX-10726
干预措施: CTX-10726 (Drug)
Dose Expansion Cohort 2
Dose of CTX-10726 depending on Cohort 1 data
干预措施: CTX-10726 (Drug)
结局指标
主要结局
Cohort 1: Evaluate the safety and tolerability of CTX-10726 by incidence of treatment-emergent adverse events (TEAEs) in escalating doses
时间窗: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until 30 days after the last dose of CTX-10726, average of 6 months)
Incidence of dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.
Cohort 1: Determine the dose(s) of CTX-10726 to be further examined in Cohort 2 and Phase 2 studies
时间窗: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks ) until 30 days after the last dose of CTX-10726 (average of 6 months)
Cohort 2: Evaluate the safety and tolerability of CTX-10726 by incidence of treatment-emergent adverse events (TEAEs) at dose(s) selected from Cohort 1
时间窗: From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until 30 days after the last dose of CTX-10726 (up to 2 years)
Incidence of treatment-emergent adverse events (TEAEs)
次要结局
- Objective Response Rate (ORR) (Percentage of Participants With Objective Response) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1(Baseline until confirmed disease progression (up to 2 years))
- Duration of Response (DOR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1(From the date of first confirmed complete response (CR) or partial response (PR) until the first date of recurrent or progressive disease (up to 2 years))
- Disease Control Rate (DCR) percentage of patients with best overall response of CR, PR, or SD as per RECIST version 1.1(From first dose of CTX-10726(Cycle 1 Day 1,Cycle = 2 weeks ) until disease progression or death, whichever occur first (up to 2 years))
- Clinical Benefit Rate (CBR) percentage of patients with best overall response of CR, PR, or SD for ≥ 6 months as per RECIST version 1.1(From first dose of CTX-10726(Cycle 1 Day 1,Cycle = 2 weeks ) until disease progression or death, whichever occur first (up to 2 years))
- Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(From first dose of CTX-10726(Cycle 1 Day 1,Cycle = 2 weeks ) until disease progression or death, whichever occur first (up to 2 years))
- Overall Survival (OS)(From first dose of CTX-10726 (Cycle 1 Day 1,Cycle = 2 weeks) until death (up to 2 years))
- Maximum serum concentration (Cmax) of CTX-10726(From first dose of CTX-10726 (Cycle 1 Day 1 = 2 weeks) until treatment discontinuation)
- Time of maximum serum concentration (Tmax) of CTX-10726(From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation)
- Trough concentration (Ctrough) of CTX-10726(From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation)
- Area under the curve (AUC) of CTX-10726(From first dose of CTX-10726 (Cycle 1 Day 1,Cycle = 2 weeks) until treatment discontinuation)
- Clearance (CL) of serum concentrations of CTX-10726(From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation)
- Volume of distribution (Vd) of serum concentrations of CTX-10726(From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation)
- Terminal elimination half-life (t1/2) of serum concentrations of CTX-10726(From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation)
- Dose response for CTX-10726(From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until treatment discontinuation)
- Assess the immunogenicity of CTX-10726 screen for the presence and development of antibodies against CTX-10726(From first dose of CTX-10726 (Cycle 1 Day 1, Cycle = 2 weeks) until end of treatment visit)