An Open-Label Multicenter Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Subjects With Advanced Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 128
- 试验地点
- 44
- 主要终点
- Part 1, Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
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 H3B-6527, and to assess the safety, tolerability and pharmacokinetics of H3B-6527.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
H3B-6527 (escalation and expansion)
Hepatocellular Carcinoma
干预措施: H3B-6527 (Drug)
结局指标
主要结局
Part 1, Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
时间窗: Cycle 1 (Cycle length = 21 days)
DLTs were defined as any of the following toxicities: Hematology, gastrointestinal, renal, hepatic or nonhematologic toxicities occurring during Cycle 1 in Dose Escalation Phase only and judged by the investigator as related to study drug. This included any Grade 4: neutropenia that does not resolve to Grade less than or equal to (\<=) 2 within 7 days, thrombocytopenia, anemia of any duration, diarrhea and/or vomiting irrespective of prophylaxis or appropriate treatment; Grade 3: thrombocytopenia requiring transfusion, thrombocytopenia and clinically significant bleeding, anemia if transfused or if lasting for more than 7 days, nausea, vomiting and/or diarrhea lasting more than 72 hours despite the use of optimal anti-emetic/antidiarrheal treatment, bilirubin, fatigue lasting less than 1 week, elevations in biochemistry laboratory values without associated clinical symptoms that last for \<=7 days; Grade greater than or equal to (\>=) 3 serum creatinine.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: From the first dose of study drug up to approximately 36.7 months
A TEAE was defined as an adverse event (AE) that emerges during treatment, having been absent at pretreatment (Baseline) or reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pretreatment state, when the AE was continuous. An SAE was any untoward medical occurrence that at any dose: Resulted in death, was life-threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug).
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
时间窗: From baseline up to approximately 36.7 months
Laboratory assessment included hematology, coagulation, clinical chemistry, and urinalysis parameters.
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters
时间窗: From baseline up to approximately 36.7 months
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters
时间窗: From baseline up to approximately 36.7 months
次要结局
- Part 2, Dose Expansion Phase: Time to Response (TTR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1(From date of first dose of study drug until CR or PR (up to approximately 36.7 months))
- Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527(Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days))
- Maximum Observed Plasma Concentration (Cmax) of H3B-6527(Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days))
- Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527(Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days))
- Part 2, Dose Expansion Phase: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1(From the first dose date until disease progression/recurrence or up to approximately 36.7 months)
- Part 2, Dose Expansion Phase: Duration of Response (DOR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1(From the date of first documented CR or PR up to approximately 36.7 months)
- Part 2, Dose Expansion Phase: Progression-free Survival (PFS) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1(From the first dose date to the date of the first documentation of PD as determined by the investigator or death (whichever occurs first) up to approximately 36.7 months)
- Part 2, Dose Expansion Phase: Overall Survival (OS)(From the date of first dose of study drug until date of death from any cause (up to approximately 36.7 months))