An Open-label Phase I Dose Finding Trial With BI 891065 Alone and in Combination With BI 754091 to Characterise Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy in Patients With Advanced and/or Metastatic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 62
- 试验地点
- 3
- 主要终点
- Part A - Maximum Tolerated Dose (MTD) of BI 891065
研究概览
简要总结
The main objective of the dose-escalation parts of the trial is to determine the maximum tolerated dose (MTD), based on the frequency of patients experiencing dose-limiting toxicities (DLTs), and/or the recommended dose for further development of BI 891065 monotherapy as well as of BI 891065 in combination with BI 754091, and to evaluate its safety and tolerability by monitoring the occurrence and severity of adverse events (AEs).
Secondary objectives are the determination of the pharmacokinetic (PK) profile of BI 891065 monotherapy as well as of BI 891065 in combination with BI 754091, and the preliminary assessment of anti-tumour activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
Part A: 50 mg BI 891065
BI 891065 alone
干预措施: BI 891065 (Drug)
Part A: 100 mg BI 891065
BI 891065 alone
干预措施: BI 891065 (Drug)
Part A: 200 mg BI 891065
BI 891065 alone
干预措施: BI 891065 (Drug)
Part A: 400 mg BI 981065
BI 891065 alone
干预措施: BI 891065 (Drug)
Part B: 50 mg BI 891065 QD + 240 mg BI 754091
BI 891065 in combination with BI 754091
干预措施: BI 891065 (Drug)
Part B: 50 mg BI 891065 QD + 240 mg BI 754091
BI 891065 in combination with BI 754091
干预措施: BI 754091 (Drug)
Part A: 5 mg BI 891065
BI 891065 alone
干预措施: BI 891065 (Drug)
Part A: 15 mg BI 891065
BI 891065 alone
干预措施: BI 891065 (Drug)
Part A: 25 mg BI 891065
BI 891065 alone
干预措施: BI 891065 (Drug)
Part B: 200 mg BI 891065 QD + 240 mg BI 754091
BI 891065 in combination with BI 754091
干预措施: BI 891065 (Drug)
Part B: 200 mg BI 891065 QD + 240 mg BI 754091
BI 891065 in combination with BI 754091
干预措施: BI 754091 (Drug)
Part B: 400 mg BI 891065 QD + 240 mg BI 754091
BI 891065 in combination with BI 754091
干预措施: BI 754091 (Drug)
Part B: 200 mg BI 981065 BID + 240 mg BI 754091
BI 891065 in combination with BI 754091
干预措施: BI 891065 (Drug)
Part B: 200 mg BI 981065 BID + 240 mg BI 754091
BI 891065 in combination with BI 754091
干预措施: BI 754091 (Drug)
结局指标
主要结局
Part A - Maximum Tolerated Dose (MTD) of BI 891065
时间窗: First treatment cycle (MTD evaluation period), up to 21 days.
Maximum tolerated dose (MTD) defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period.
Part A - Number of Patients With Dose-limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period
时间窗: First treatment cycle (MTD evaluation period), up to 21 days.
DLT is defined as: Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for \>5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease. Non-hematological toxicities: AST or ALT \>3xULN and concurrent total bilirubin \>2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.
Part B: Maximum Tolerated Dose (MTD) of BI 891065 in Combination With Ezabenlimab
时间窗: First treatment cycle (MTD evaluation period), up to 21 days.
Maximum tolerated dose (MTD) of BI 891065 in combination with ezabenlimab, defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period.
Part B: Number of Patients With Dose-limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period
时间窗: First treatment cycle (MTD evaluation period), up to 21 days.
DLT is defined as: Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for \>5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease. Non-hematological toxicities: AST or ALT \>3xULN and concurrent total bilirubin \>2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.
次要结局
- Part A: Number of Patients With Dose-limiting Toxicities (DLT) During the Entire On-treatment Period(From first drug administration until last drug administration plus residual effect period of 30 days, up to 282 days.)
- Part A: Number of Patients With Objective Response (OR)(Up to 252 days.)
- Part A: Maximum Measured Plasma Concentration of BI 891065 at Steady State (Cmax,ss)(Just before drug intake and 0.5**, 1, 2, 3, 4*, 5, 6, 7, 8, 10**, 12*, 24, 36, 47.917, 167.917, 263.917, 335.917, 336.5**, 337, 338, 339, 340*, 341, 342, 343, 344, 346**, 348*, 359.917 hours after drug administration on day 1.)
- Part A: Area Under the Concentration Time Curve of BI 891065 Over a Dosing Interval at Steady State (AUCtau,ss)(Just before drug intake and 0.5**, 1, 2, 3, 4*, 5, 6, 7, 8, 10**, 12*, 24, 36, 47.917, 167.917, 263.917, 335.917, 336.5**, 337, 338, 339, 340*, 341, 342, 343, 344, 346**, 348*, 359.917 hours after drug administration on day 1.)
- Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(Just before drug intake and 0.5**, 1, 2, 3, 4*, 5, 6, 7, 8, 10**, 12*, 24, 36, 47.917, 167.917, 263.917, 335.917, 336.5**, 337, 338, 339, 340*, 341, 342, 343, 344, 346**, 348*, 359.917 hours after drug administration on day 1.)
- Part B: Number of Patients With Dose-limiting Toxicities (DLTs) Observed During the Entire Treatment Period(From first drug administration until last drug administration plus residual effect period of 30 days, up to 386 days.)
- Part B: Number of Patients With Objective Response (OR)(Up to 356 days.)
- Part B: Area Under the Concentration-time Curve of BI 891065 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(At 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 336.5, 337, 338, 339, 341, 342, 343, 344, 346, 359.5, 360.5, 361, 362, 363, 365, 366, 367, 368, 370 and 383.917 hours after intake of BI 891065 at day 1, cycle 1.)
- Part B: Area Under the Concentration Time Curve of BI 891065 Over a Dosing Interval at Steady State (AUCtau,ss)(At 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 336.5, 337, 338, 339, 341, 342, 343, 344, 346, 359.5, 360.5, 361, 362, 363, 365, 366, 367, 368, 370 and 383.917 hours after intake of BI 891065 at day 1, cycle 1.)
- Part B: Maximum Measured Plasma Concentration of BI 891065 at Steady State (Cmax,ss)(At 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 336.5, 337, 338, 339, 341, 342, 343, 344, 346, 359.5, 360.5, 361, 362, 363, 365, 366, 367, 368, 370 and 383.917 hours after intake of BI 891065 at day 1, cycle 1.)
- Part B: Maximum Measured Plasma Concentration (Cmax) of BI 754091 in the First Treatment Cycle(Predose and 1, 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 359.5, 383.917, 504, 998 and 999 hours after intake of BI 754091 at day 1, cycle 1.)
- Part B: Area Under the Concentration-time Curve of BI 754091 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(Predose and 1, 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 359.5, 383.917, 504, 998 and 999 hours after intake of BI 754091 at day 1, cycle 1.)