A Multi-center, Open-label, Phase 1/2a Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of KAT-101 in Subjects With HCC
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 发起方
- 入组人数
- 148
- 试验地点
- 3
- 主要终点
- To determine the Recommended Phase 2 Dose (RP2D) for oral + IT administration
研究概览
简要总结
NLP-KAT-101 is a Phase 1/2a dose escalation and expansion study to investigate the safety, tolerability, PK, and preliminary efficacy of oral + intratumoral (IT) KAT in subjects with HCC.
详细描述
Phase 1 will identify the optimal dose for oral alone, IT alone and the recommended Phase 2 dose (RP2D) dose for oral + IT together. Once the RP2D is identified, additional subjects will be enrolled into Phase 2a (dose-expansion) to further investigate the efficacy and safety of oral + IT KAT at the RP2D.
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
- •Confirmed HCC not amenable to surgical resection or curative-intent locoregional ablative treatments and who are not eligible for liver transplantation.
- •Systemic treatment-naive for unresectable locally advanced or metastatic HCC. In addition, have progressed on, refused or were intolerant to sorafenib, lenvatinib, or atezolizumab in combination with bevacizumab. A maximum of 2 prior lines of systemic therapy (including chemotherapy or targeted therapy, not including locoregional therapy) will be allowed.
- •At least one measurable lesion based on RECIST 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Adequate organ function
排除标准
- •Prior to the first administration of the study treatment:
- •Major surgery within 28 days
- •Radiotherapy within 14 days including palliative radiation
- •Use of steroids (except for topical agents) within 14 days
- •Chemotherapy within 3 weeks (6 weeks for nitrosourea compounds)
- •Prior treatment with biologic agents, including hormone therapy, within the last 3 weeks, or at least 5 half-lives, whichever is shorter
- •Tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver
- •Treatment with another investigational product within 4 weeks prior to screening or for which 5 half-lives have not elapsed, whichever is longer
- •Uncontrolled central nervous system (CNS) metastasis
- •Any clinically significant abnormal intestinal findings that may interfere with the investigational product
- •Severe cardiac disorders or subjects with comorbidities of other serious internal disorders on investigator's judgment
- •QTcF > 450 msec or congenital long QT syndrome
- •Suspected serious infectious diseases, intestinal paralysis, bowel obstruction, interstitial pneumonia, or pulmonary fibrosis
- •Serious underlying medical or psychiatric condition, dementia or altered mental status that would impair the ability to understand informed consent, contraindicate participation in the study or confound the results of the study
- •Known human immunodeficiency virus (HIV) infection or chronic or active hepatitis B virus (HBV) hepatitis C virus (HCV). Subjects with HCV who have a documented cure (undetectable HCV ribonucleic acid (RNA) 24 weeks after the end of treatment) may be enrolled.
- •Severe physical or mental trauma that results from injury or a wound(s).
- •Any condition or non-removable device contraindicated for MRI examination
- •Pregnant women or nursing mothers.
- •Women of childbearing potential (WOCBP) who are unwilling to use a medically acceptable method of birth control during the study until 185 days after the last dose of study treatment
- •Men with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the study until 95 days after the last dose of study treatment.
研究组 & 干预措施
Oral experimental arm
Oral administration (KAT-101) taken once per day for 4 consecutive days out of 7 (4 days on / 3 days off weekly). Each cycle is 28 days. Treatment will continue for up to 12 cycles until progressive disease (PD), unacceptable toxicity, or any reason for discontinuing its administration, whichever occurs first.
干预措施: KAT-101 (Drug)
IT experimental arm
IT administration (KAT-201) will be injected via percutaneous IT injection with ultrasound and/or computed tomography (CT) guidance once a week (on Day 1 weekly). Each cycle is 28 days. Treatment will continue for up to 2 cycles until PD, unacceptable toxicity, or any reason for discontinuing its administration, whichever occurs first.
干预措施: KAT-201 (Drug)
Oral + IT experimental arm
Once optimal oral and IT dose are determined, oral + IT will be administered as follows: oral administration (KAT-101) will be taken once per day for 4 consecutive days out of 7 (4 days on / 3 days off weekly). Treatment will continue for up to 12 cycles (each cycle 28 days). IT administration (KAT-201) will be injected via percutaneous IT injection with ultrasound and/or CT guidance once a week (on Day 1 weekly). Treatment will continue for up to 2 cycles (each cycle 28 days) until PD, unacceptable toxicity, or any reason for discontinuing its administration, whichever occurs first.
干预措施: KAT-101 (Drug)
Oral + IT experimental arm
Once optimal oral and IT dose are determined, oral + IT will be administered as follows: oral administration (KAT-101) will be taken once per day for 4 consecutive days out of 7 (4 days on / 3 days off weekly). Treatment will continue for up to 12 cycles (each cycle 28 days). IT administration (KAT-201) will be injected via percutaneous IT injection with ultrasound and/or CT guidance once a week (on Day 1 weekly). Treatment will continue for up to 2 cycles (each cycle 28 days) until PD, unacceptable toxicity, or any reason for discontinuing its administration, whichever occurs first.
干预措施: KAT-201 (Drug)
结局指标
主要结局
To determine the Recommended Phase 2 Dose (RP2D) for oral + IT administration
时间窗: 24 months
RP2D is defined as the dose at which dose escalation (oral + IT) ceases
次要结局
- To evaluate the preliminary anti-tumor activity of KAT for oral + IT administration(54 months)
- To assess area under the curve (AUC) of KAT (oral and oral + IT)(54 months)
- To assess half lives (T1/2) of KAT (oral and oral + IT)(54 months)
- To evaluate the safety and tolerability of KAT (oral, IT, and oral + IT) in subjects with HCC(54 months)
- To assess maximum concentration (Cmax) of KAT (oral and oral + IT)(54 months)
- To assess median time to the maximum drug concentration (Tmax) of KAT (oral and oral + IT)(54 months)