A Phase I Open-Label Study of the Safety and Tolerability of ATG-019, a Dual Inhibitor of PAK4 and NAMPT, in Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 8
- 主要终点
- To determine MTD* or RP2D*
研究概览
简要总结
This is a multi-center, open-label clinical study with separate Dose Escalation and Expansion Phases to assess preliminary safety, tolerability, and efficacy of ATG-019, a dual inhibitor of PAK4 and NAMPT, alone or co-administered with starting dose of 500 mg niacin ER in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL).
详细描述
This is a multi-center, open-label clinical study with separate Dose Escalation and Expansion Phases to assess preliminary safety, tolerability, and efficacy of ATG-019, a dual inhibitor of PAK4 and NAMPT, alone or co-administered with starting dose of 500 mg niacin ER (may be titrated to 1,000 mg of daily dose, per label), in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL) for which all standard therapeutic options considered useful by the investigator have been exhausted and with PD at study entry. The MTD and RP2D will be determined.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Written informed consent obtained prior to any screening procedures and in accordance with local and institutional guidelines.
- •Age ≥18 years.
- •Patients with histologically or cytologically confirmed, NHL or advanced solid tumors which have progressed despite standard therapy, for whom no standard therapy exists, or who have refused standard therapy.
- •Patients must have objective evidence of PD on study entry:
- •Advanced solid tumors: Measureable disease as defined by RECIST 1.
- •NHL: Measureable disease including target lesion(s) as defined by the Cheson 2014 Classification2 for initial evaluation and staging.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Adequate hepatic function.
- •Adequate renal function.
- •Life expectancy of ≥ 3 months.
- •Adequate hematopoietic function.
- •Female patients of child-bearing potential must agree to use dual methods of contraception (including one highly effective and one effective method of contraception) and have a negative serum pregnancy test at Screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential.
排除标准
- •Female patients who are pregnant or lactating.
- •Time since the last prior therapy for treatment of advanced solid tumors or NHL**:
- •Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including investigational anti-cancer therapy ≤ 4 weeks prior to C1D
- •Palliative steroids for disease related symptoms within 7 days prior to C1D
- •Known central nervous system metastases.
- •Major surgery within 4 weeks before C1D
- •Impaired cardiac function or clinically significant cardiac diseases.
- •Active infection with completion of therapeutic antibiotics, antivirals, or antifungals within 1 week prior to C1D
- •Patients diagnosed with tuberculosis and had received treatment.
- •Patients with a known history of human immunodeficiency virus (HIV).
- •Known, active hepatitis A, B, or C infection.
- •Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent.
研究组 & 干预措施
ATG-019 Alone
A starting does of 30 mg QoD×3 ATG-019
干预措施: ATG-019 (Drug)
ATG-019 + Niacin ER
A starting dose of 60 mg ATG-019 and 500 mg niacin ER
干预措施: ATG-019 + Niacin ER (Combination Product)
结局指标
主要结局
To determine MTD* or RP2D*
时间窗: 18 months
MTD will be evaluated using the NCI-CTCAE, Version 5.0; RP2D will be determined by SMC for dose escalation phase.
To evaluate the Dose-Limiting Toxicity (DLT) for dose escalation phase
时间窗: 18 months
DLTs will be evaluated using the CTCAE, Version 5.0 for grading.
Overall Response Rate (ORR)
时间窗: 18 months
ORR analysis will be performed for both study phases by calculating the point estimate of the percentage of patients who have either CR or PR, presented as the number and percentage of patients, including a two-sided 95% CI.
次要结局
- Progression-free survival (PFS)(18 months)
- Time to Reach Cmax （Tmax）(18 months)
- Duration of response (DOR)(18 months)
- Disease control rate (DCR)(18 months)
- Time to progression (TTP)(18 months)
- Peak Plasma Concentration (Cmax)(18 months)
- To determine RP2D*(18 months)
- Overall Survival (OS)(18 months)