NCT05268666招募中1 期
A First-in-Human, Open-label, Dose Escalation and Expansion Study of Orally Administered JBI-802 in Patients With Advanced Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 126
- 试验地点
- 4
- 主要终点
- Investigator-Assessed ORR (Part 2)
研究概览
简要总结
The purpose of this study is to determine the maximum-tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JBI-802 in patients with Advanced Solid Tumors.The efficacy of the RP2D will be evaluated in phase 2 in patients with solid tumors of neuroendocrine differentiation.
详细描述
This is a multi-center, first in human, open-label, 2-part, dose escalation and expansion study to define safety, tolerability, maximum tolerated dose, pharmacologically active dose, assess preliminary efficacy, and explore predictive and pharmacodynamic biomarkers in up to 126 participants with advanced solid tumors. Expansion cohorts of participants, treated at the RP2D, with small cell lung cancer (SCLC), neuroendocrine prostate cancer (NEPC), and other neuroendocrine-derived cancers will be enrolled to obtain additional safety and efficacy data. Starting dose will be 10 mg orally once daily, 4 days on and 3 days off cycle.
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
- •Males or females aged ≥18 years at Screening
- •Absolute neutrophil count (ANC) ≥1500 cells/mm
- •Platelet count ≥100,000 cells/mm
- •Total bilirubin ≤1.5×ULN. Patients with Gilbert's syndrome may be enrolled with up to 3.0xULN.
- •AST and ALT ≤2.5×ULN (unless liver metastases are present then up to 5×ULN is allowed).
- •Calculated creatinine clearance (CrCL) ≥60 mL/min (Cockcroft-Gault formula).
- •Prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5×ULN if participant is not anticoagulated (Note: If participant is on anticoagulants, the participant must be on a stable dose for at least 2 weeks prior to study entry.
- •Must have at least one measurable lesion on CT scan or MRI per RECIST 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
- •Other criteria may apply
- •Participants with a histologically confirmed diagnosis of locally advanced or metastatic solid tumors (except microsatellite stable colorectal cancer and hepatocellular carcinoma) who have no available effective therapeutic options.
- •Small cell lung cancer: Participants must have a histologic diagnosis of advanced SCLC not amenable to curative therapy and have received ≤2 prior regimens, which must have included a checkpoint inhibitor and a platinum-based chemotherapy.
- •De novo or treatment-emergent NEPC
- •Basket of neuroendocrine-derived tumors, excluding SCLC and treatment-induced NEPC. Participants must have unresectable locally advanced or metastatic disease and have no available effective therapeutic options.
排除标准
- •Known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases - defined as metastasis having no evidence of progression or hemorrhage for at least 4 weeks after treatment (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of symptomatic brain metastases for at least 14 days prior to enrollment.
- •Severe or unstable medical condition, such as congestive heart failure (New York Heart Association [NYHA] Class III or Class IV), ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, psychiatric condition, as well as an uncontrolled cardiac arrhythmia requiring medication (≥Grade 2, according to NCI CTCAE Version 5), myocardial infarction within 6 months prior to starting study treatment, or any other significant or unstable concurrent cardiac illness. Note: Stable chronic atrial fibrillation is allowed.
- •Use of strong inhibitors of CYP3A within 14 days or 5 half-lives (whichever is longer) or grapefruit juice or grapefruit containing products within 7 days prior to Cycle 1 Day
- •Use of strong inducers of CYP3A within 14 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day
- •Use of strong inhibitors of cytochrome CYP2D6 within 14 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day
- •Use of strong inducers of CYP2D6 within 14 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day
- •History of other previous or concurrent cancer that would interfere with the determination of safety or efficacy assessment
- •Surgery (eg, stomach bypass) or medical condition that might significantly affect absorption of medicines
- •Other criteria may apply
研究组 & 干预措施
JBI-802
Experimental
10 mg JBI-802 once daily as the starting dose with 4 days on/3 days off cycle
干预措施: JBI-802 (Drug)
结局指标
主要结局
Investigator-Assessed ORR (Part 2)
时间窗: Up to 30 days from the last dose of study drug
Defined as either complete response (CR) or partial response (PR) as defined by RECIST version 1.1
Maximum-Tolerated Dose (MTD)
时间窗: 28-day cycle
次要结局
- Tmax: Time of Maximum Plasma Concentration JBI-802(Baseline up to 28 days from the last dose of study drug)
- Vd/F: Apparent Volume of Distribution During Terminal Phase (Vz/F) After Oral Administration calculated as (CL/F)/ Ke(Baseline up to 28 days from the last dose of study drug)
- Investigator-Assessed Overall Response Rate (ORR) (Part 1)(Up to 30 days from the last dose of study drug)
- Incidence of AEs(Up to 30 days from the last dose of study drug)
- CL/F: Apparent Oral Clearance (CL/F) computed as Dose/AUC(Baseline up to 28 days from the last dose of study drug)
- t½: The Apparent Terminal Elimination Half-life JBI-802(Baseline up to 28 days from the last dose of study drug)
- PSA 50 Response Rate in Patients with Prostate Cancer(Baseline up to 30 days from the last dose of study drug)
- Clast: Last Observed (quantifiable) Plasma Concentration in units of ng/mL JBI-802(Baseline up to 28 days from the last dose of study drug)
- OS: Overall Survival(Date patient started study drug to date of death for any cause, assessed up to 30 months)
- AUC(0-last): Area Under the Concentration-time Curve from Dosing (time 0) to Time of Last Measured Concentration JBI-802(Baseline up to 28 days from the last dose of study drug)
- AUC(0-t) (partial AUC): Area Under the Concentration-time Curve from Dosing (time 0) to Time t JBI-802(Baseline up to 28 days from the last dose of study drug)
- Cmax: Maximum Plasma Concentration JBI-802(Baseline up to 28 days from the last dose of study drug)
- Duration of Response (DOR)(Up to 30 days from the last dose of study drug)
- PFS: Progression Free Survival(Date patient started study drug to date of progression, assessed up to 30 months)
研究者
研究点 (4)
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