A Phase 1/2a, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-2485 in Adult Patients With Advanced Solid Tumors
概览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 102
- 试验地点
- 10
- 主要终点
- Dose Escalation phase: Number of participants with dose limiting toxicities (DLTs)
概览
简要总结
This study is to evaluate the safety and tolerability of JAB-2485 monotherapy in adult participants with advanced solid tumors.
详细描述
The primary objective of this study is to evaluate the safety and tolerability of JAB-2485 monotherapy to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) during Dose Escalation phase when administered in participants with advanced solid tumors; then to further evaluate preliminary antitumor activity of JAB-2485 monotherapy at the RP2D during Dose Expansion phase in patients with advanced solid tumors such as ER+ breast cancer, triple negative breast cancer (TNBC), AT-rich interaction domain 1A (ARID1A) mutant solid tumors and small cell lung cancer (SCLC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Must be able to provide an archived tumor sample
- •Must have histologically or cytologically confirmed metastatic or locally advanced solid tumor
- •Dose Expansion phase cohorts must meet specific expression or gene mutation where indicated
- •Must be refractory to or become intolerant of existing therapy(ies) known to provide clinical benefit for their condition
- •Must have at least 1 measurable lesion per RECIST v1.1
- •Must have adequate organ functions
- •Must be able to swallow and retain orally administered medication
排除标准
- •Has central nervous system (CNS) metastases or carcinomatous meningitis, except if CNS metastases treated and no evidence of radiographic progression or hemorrhage for at least 28 days
- •Active infection requiring systemic treatment within 7 days
- •Active hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV
- •Any severe and/or uncontrolled medical conditions
- •left ventricular ejection fraction (LVEF) ≤50% assessed by echocardiogram (ECHO) or multigated acquisition scan (MUGA)
- •QT interval using Fridericia's formula (QTcF) interval \>470 msec
- •Experiencing unresolved CTCAE 5.0 Grade \>1 toxicities
- •Clinically significant eye disorders
研究组 & 干预措施
JAB-2485 monotherapy, Phase 1, Dose Escalation
Dose escalation of JAB-2485 will be administered as monotherapy to determine the MTD and RP2D.
干预措施: JAB-2485 (Aurora A inhibitor) (Drug)
JAB-2485 monotherapy, Phase 2a, Dose Expansion
JAB-2485 will be administered as monotherapy in patients with specific tumor types to evaluate the preliminary antitumor activity.
干预措施: JAB-2485 (Aurora A inhibitor) (Drug)
结局指标
主要结局
Dose Escalation phase: Number of participants with dose limiting toxicities (DLTs)
时间窗: First 21 days of Cycle 1
A DLT is defined as an adverse event (AE) regardless of attribution unless clearly related to underlying disease or extraneous cause during the first 21 days of Cycle 1 (DLT observation period).
Dose Expansion phase: Objective Response Rate (ORR)
时间窗: Up to 3 years from baseline to RECIST confirmed Progressive Disease (PD)
ORR is defined as the percentage of participants with partial response (PR) or complete response (CR) based on RECIST v1.1
Dose Escalation phase: Number of participants with adverse events (AEs)
时间窗: Up to 3 years
Participants will be assessed for incidence and severity of AEs according to NCI-CTCAE v5.0
Dose Expansion phase: Duration of Response (DOR)
时间窗: Up to 3 years
DOR is defined as the time from the participants initial objective response (CR or PR) to disease progression per CTCAE v1.1 or death due to any cause, whichever occurs first.
次要结局
- Dose Escalation phase: Duration of Response (DOR)(Up to 3 years)
- Dose Escalation and Dose Expansion phase: peak plasma concentration (Cmax)(Up to 3 years)
- Dose Escalation and Dose Expansion phase: time to peak plasma concentration(Tmax)(Up to 3 years)
- Dose Escalation and Dose Expansion phase: Ctrough(Up to 3 years)
- Dose Escalation and Dose Expansion phase: Area under the curve (AUC)(Up to 3 years)
- Dose Escalation and Dose Expansion phase: half-life (t½)(Up to 3 years)
- Dose Escalation phase: Objective Response Rate (ORR)(Up to 3 years from baseline to RECIST confirmed Progressive Disease (PD))
- Dose Escalation and Dose Expansion phase: Time to response (TTR)(Up to 3 years)
- Dose Escalation and Dose Expansion phase: total body clearance(Up to 3 years)
- Dose Expansion phase: Progression Free Survival (PFS)(Up to 3 years)
- Dose Expansion Phase 2a: Overall Survival (OS)(Up to 3 years)
- Dose Expansion phase: Disease Control Rate (DCR)(Up to 3 years)
- Dose Expansion phase: Number of participants with adverse events (AEs)(Up to 3 years)