A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread
- Conditions
- NeoplasmsNeoplasm MetastasisCarcinoma, Non-Small-Cell Lung
- Interventions
- Drug: BI 891065Drug: BI 754091
- Registration Number
- NCT03166631
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 62
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part A: 100 mg BI 891065 BI 891065 BI 891065 alone Part A: 200 mg BI 891065 BI 891065 BI 891065 alone Part A: 400 mg BI 981065 BI 891065 BI 891065 alone Part B: 50 mg BI 891065 QD + 240 mg BI 754091 BI 891065 BI 891065 in combination with BI 754091 Part B: 50 mg BI 891065 QD + 240 mg BI 754091 BI 754091 BI 891065 in combination with BI 754091 Part B: 200 mg BI 891065 QD + 240 mg BI 754091 BI 891065 BI 891065 in combination with BI 754091 Part B: 200 mg BI 891065 QD + 240 mg BI 754091 BI 754091 BI 891065 in combination with BI 754091 Part B: 400 mg BI 891065 QD + 240 mg BI 754091 BI 754091 BI 891065 in combination with BI 754091 Part B: 200 mg BI 981065 BID + 240 mg BI 754091 BI 891065 BI 891065 in combination with BI 754091 Part B: 200 mg BI 981065 BID + 240 mg BI 754091 BI 754091 BI 891065 in combination with BI 754091 Part A: 5 mg BI 891065 BI 891065 BI 891065 alone Part A: 15 mg BI 891065 BI 891065 BI 891065 alone Part A: 25 mg BI 891065 BI 891065 BI 891065 alone Part A: 50 mg BI 891065 BI 891065 BI 891065 alone
- Primary Outcome Measures
Name Time Method Part A - Maximum Tolerated Dose (MTD) of BI 891065 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 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 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 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.
- Secondary Outcome Measures
Name Time Method 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. 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 A: Number of Patients With Objective Response (OR) Up to 252 days. OR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, defined as the best overall response of complete response (CR) and partial response (PR), where the best overall response is the best time point response recorded from the first administration of study medication until the end of treatment Number of patients with objective response is reported.
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. Maximum measured plasma concentration at steady state (cmax,ss) during the first treatment cycle.
Timeframe description:
\*: Timepoint measured only for dose group 5 mg, 15 mg, 25 mg, and 50 mg.
\*\*: Timepoint measured only for dose group 50 mg, 100 mg, 200 mg and 400 mg.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. Area under the concentration time curve of BI 891065 over a dosing interval at steady state (AUCtau,ss).
Timeframe description:
\*: Timepoint measured only for dose group 5 mg, 15 mg, 25 mg, and 50 mg.
\*\*: Timepoint measured only for dose group 50 mg, 100 mg, 200 mg and 400 mg.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. 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) in the first treatment cycle.
Timeframe description:
\*: Timepoint measured only for dose group 5 mg, 15 mg, 25 mg, and 50 mg.
\*\*: Timepoint measured only for dose group 50 mg, 100 mg, 200 mg and 400 mg.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. 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: Number of Patients With Objective Response (OR) Up to 356 days. OR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, defined as the best overall response of complete response (CR) and partial response (PR), where the best overall response is the best time point response recorded from the first administration of study medication until the end of treatment. Number of patients with objective response is reported.
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. 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) in the first treatment cycle.
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. Area under the concentration time curve of BI 891065 over a dosing interval at steady state (AUCtau,ss) in the first treatment cycle.
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. Maximum measured plasma concentration of BI 891065 at steady state (Cmax,ss) in the first treatment cycle.
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. Maximum measured plasma concentration (Cmax) of BI 754091 in the first treatment cycle.
Results are reported for the overall group only since dose level of BI 754091 is fixed in this trial.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. 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) in the first treatment cycle.
Results are reported for the overall group only since dose level of BI 754091 is fixed in this trial.
Trial Locations
- Locations (3)
Froedtert and The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States