Phase 1, Dose Escalation, Safety, Tolerability, and Pharmacokinetic Study of SR-8541A (ENPP1 Inhibitor) Administered Orally as Monotherapy or in Combination With Checkpoint Inhibitors in Subjects With Advanced/Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 25
- 试验地点
- 3
- 主要终点
- Recommended Phase 2 Dose (RP2D) of SR-8541A
研究概览
简要总结
This is an open-label, dose-escalation, multi-center phase 1 study evaluating the safety, tolerability, and pharmacokinetics (PK) of SR-8541A administered orally as a monotherapy or in combination with an immune checkpoint inhibitor (ICI) in subjects with solid tumors.
详细描述
SR-8541A, an ENPP1 inhibitor, will be administered orally as a monotherapy to assess safety, tolerability, and pharmacokinetics (PK) in subjects with advanced/metastatic solid tumors.
Subjects eligible for treatment include those whose disease is refractory to standard therapeutic options, or for which there are no standard therapeutic options available.
All enrolled patients will orally administer SR-8541A daily. Treatment may continue until the subject's disease worsens or another treatment discontinuation criterion is met.
The combination part will only commence once the SRC has deemed it safe to proceed and a SR-8541A dose from the dose escalation part is selected as the RP2D. The ICI will be either nivolumab or pembrolizumab and dosing will be per SOC. Both investigational products will start on C1D1. Treatment with ICI may be continued if SR-8541A is discontinued and treatment with SR-8541A may be continued after ICI is discontinued.
Approximately 10 subjects will be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Life expectancy of at least 3 months
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
- •Histopathologically/cytologically confirmed advanced solid tumor, which is refractory to standard therapeutic options, or for which there are no standard therapeutic options.
- •Measurable disease per RECIST v1.1
- •Willing to provide archival or fresh tumor tissue during screening (required) and post-treatment (optional)
- •Adequate hematologic, renal and hepatic function
排除标准
- •Primary central nervous system (CNS) tumor
- •Prior systemic anti-cancer treatment including other investigational agents, surgery, or radiation within 28 days or 5 half-lives, whichever is less
- •Continuous systemic treatment with either corticosteroids (>10 milligram [mg] daily prednisone equivalents) or other immunosuppressive medications within 28 days
- •Active autoimmune disease that has required systemic treatment in past 2 years
- •History of documented congestive heart failure (New York Heart Association [NYHA] class II - IV); unstable angina; poorly controlled hypertension; clinically significant valvular heart disease; high-risk uncontrolled arrhythmias (including sustained ventricular tachycardia); myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack within the last 6 months, or Canadian Cardiovascular Society angina class > 2
- •Troponin I > ULN
- •Blood pressure (BP) - Systolic < 95 mmHg or > 160 mmHg or diastolic > 100 mmHg
- •Resting heart rate (HR) > 100 beats per minute (BPM)
- •Corrected QT interval by Fridericia (QTcF) ≥ 470 ms
- •Left Ventricular Ejection Fraction (LVEF) < 50%
- •Symptomatic uncontrolled CNS disease requiring treatment with steroids or anti-seizure medications within 2 months
- •Leptomeningeal disease
- •Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 8 weeks
- •Bleeding diathesis due to underlying medical condition or anticoagulation medication which is unable to be promptly reversed by medical treatment
- •Prior additional malignancy that is progressing or has received treatment the previous 3 years
- •Active infection requiring systemic treatment
- •Positive for human immunodeficiency virus (HIV) (HIV antibodies) or active hepatitis B (e.g., HbsAg reactive) or active hepatitis C (e.g., HCV ribonucleic acid [RNA] qualitative) infection with detectable viral load
- •Major surgery within 28 days prior to Day 1 and/or minor surgery (excluding biopsy) within 7 days
研究组 & 干预措施
SR-8541A Monotherapy
SR-8541A will be orally administered.
干预措施: SR-8541A (Drug)
SR-8541A Monotherapy
SR-8541A will be orally administered.
干预措施: Immune checkpoint inhibitor (ICI) (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D) of SR-8541A
时间窗: From first dose of study drug through 28 days following the first dose of study treatment
Based on evaluation of Dose Limiting Toxicities (DLT)
Frequency and severity of Adverse Events
时间窗: From first dose of study drug through 30 days following the last dose of study treatment
Adverse events will be graded according to CTCAE v5.0.
次要结局
- Area under the curve from zero up to time t (AUC0-t)(From first dose of study drug through 28 days following the first dose of study treatment)
- Terminal phase rate constant (λz)(From first dose of study drug through 28 days following the first dose of study treatment)
- Maximum plasma concentration (Cmax)(From first dose of study drug through 28 days following the first dose of study treatment)
- Progression Free Survival(From first dose of study drug through 2 years following first dose)
- Area under the concentration time curve from time 0 extrapolated to infinity (AUC0-inf)(From first dose of study drug through 28 days following the first dose of study treatment)
- Maximal time for peak concentration (Tmax)(From first dose of study drug through 28 days following the first dose of study treatment)
- Half-life (t1/2)(From first dose of study drug through 28 days following the first dose of study treatment)
- Duration of Response(From first dose of study drug through 2 years following first dose)
- Overall Response Rate(From first dose of study drug through 2 years following first dose)
- Overall Survival(From first dose of study drug through 2 years following first dose)
- Disease Control Rate(From first dose of study drug through 2 years following first dose)