Phase 1a - Explore safety and establish the maximum tolerated dose (MTD)/recommended dose levels for phase Ib expansion phase of BI 905711 based on the frequency of patients experiencing dose limiting toxicities (DLTs) during the MTD evaluation period. The MTD evaluation period is defined as the first two treatment cycles (from first dose administration until the day preceding the third dose administration or end of REP in case of discontinuation before start of Cycle 3). Phase 1a - Explore pharmacokinetics/pharmacodynamics, and efficacy to guide the determination of a potentially effective dose range for phase Ib in the absence of MTD. Phase 1b - Evaluate efficacy and safety of BI 905711 at a potentially effective dose range and determine the Recommended Phase 2 Dose (RP2D)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
110
BI 905711
Yale Cancer Center
New Haven, Connecticut, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
START South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, United States
Brussels - UNIV Saint-Luc
Brussels, Belgium
UZ Leuven
Leuven, Belgium
Beijing Cancer Hospital
Beijing, China
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou, China
HOP Jean Minjoz
Besançon, France
CTR Leon Berard
Lyon, France
...and 8 more locations
Maximum Tolerated Dose (MTD) of BI 905711 in Phase 1a
Maximum tolerated dose (MTD) was defined as the highest dose with less than 25% risk of the true drug limiting dose (DLT) rate being equal to or above 33% during the MTD evaluation period. The MTD was to be considered reached if one of the following criteria was fulfilled: the posterior probability of the true DLT rate in the target interval (0.16, 0.33) of the MTD is above 0.5 or at least 15 patients have been treated in phase 1a, of which at least 6 were at the MTD.
Time frame: From cycle 1 Day 1 until the second administration of study treatment (two 14-day treatment cycles).
Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a
Number of patients with dose-limiting toxicity (DLT) during the MTD evaluation period is reported.
Time frame: From cycle 1 Day 1 until the day before cycle 3 Day 1 (two 14-day treatment cycles).
Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined
Confirmed objective response (OR) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in patients with measurable disease is reported. This was defined as the best overall response of complete response (CR) or partial response (PR), where best overall response was the best response recorded from the start of the study treatment until the earliest of disease progression, death, or last evaluable tumor assessment and before start of subsequent anticancer therapy.
Time frame: From the first administration of trial medication until the earliest of progressive disease (PD), death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, up to 48 weeks.
Progression-free Survival (PFS)
This was evaluated per RECIST 1.1 criteria for target lesions and assessed by CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. Overall response at each time point was evaluated by target lesion, non-target lesions and new lesions together, according to RECIST 1.1. Objective response (OR) was defined as best overall response of confirmed CR or confirmed PR according to RECIST 1.1.
Time frame: From the first administration of trial medication until tumor progression or death, whichever occurred first, up to 48 weeks.
Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a
Maximum measured plasma concentration (Cmax) of BI 905711 during the first cycle in phase 1a is reported.
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1.
Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a
Maximum measured plasma concentration (Cmax) of BI 905711 during the third cycle in phase 1a is reported.
Time frame: Cycle 3: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the First Cycle in Phase 1a
Area under the concentration-time curve (AUC0-336) of BI 905711 during the first cycle in phase 1a is reported.
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1 .
Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the Third Cycle in Phase 1a
Area under the concentration-time curve (AUC0-336) of BI 905711 during the third cycle in phase 1a is reported.
Time frame: Cycle 3: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1b
Maximum measured plasma concentration (Cmax) of BI 905711 during the first cycle in phase 1b is reported.
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
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Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1b
Maximum measured plasma concentration (Cmax) of BI 905711 during the third cycle in phase 1b is reported.
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the First Cycle in Phase 1b
Area under the concentration-time curve (AUC0-336) in plasma of BI 905711 during the first cycle in phase 1b is reported. 11. The AUC calculation includes an extrapolation from 168 hrs to 336 hrs to account for the weekly dosing schedule.
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the Third Cycle in Phase 1b
Area under the concentration-time curve (AUC0-336) in plasma of BI 905711 during the third cycle in phase 1b is reported. The AUC calculation includes an extrapolation from 168 hrs to 336 hrs to account for the weekly dosing schedule.
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
Number of Patients With Treatment-emergent Adverse Events (AEs)
The number of patients with treatment-emergent adverse events (AEs) is reported, namely, all adverse events occurring between start of treatment and end of the residual effect period (REP). Adverse events that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.
Time frame: From start of treatment until the last dose of trial medication plus the residual effect period (REP), up to 358 days.
Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters
Radiological (CT scan) tumor shrinkage, defined as the difference between the minimum post-baseline sum of longest diameters of target lesions and the baseline sum of the longest diameters of the same set of target lesions according to RECIST 1.1 is reported. Negative values indicate a reduction in the sum of target lesion diameters and positive values indicate an increase.
Time frame: At baseline and every 8 weeks (± 7 days) until progression or start of further treatment for disease, up to 48 weeks.
Duration of Overall Response
The duration of overall response was measured from the time measurement criteria were first met for complete response (CR) / partial response (PR) (whichever was first recorded) until the first date that recurrent or progression disease (PD) was objectively documented (taking as reference for PD the smallest measurements recorded in the study) according to RECIST 1.1.
Time frame: From the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or PD is objectively documented, up to 48 weeks.
Disease Control
Disease control was defined as complete response (PR), partial response (PR), or stable disease according to RECIST 1.1 from the start of treatment until the earliest of progression disease (PD), death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy. This endpoint analyzed the number of patients meeting this criterion.
Time frame: From the start of treatment until the earliest of PD, death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy, up to 48 weeks.