Cholangiocarcinoma, Gastrointestinal Neoplasms, Pancreatic Neoplasms
Conditions
Brief summary
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)
Interventions
DRUGBI 905711
BI 905711
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1a: Dose escalation (non randomised) Phase 1b: Dose expansion (randomised)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- a. Phase Ia (dose escalation only) Histologically or cytologically confirmed, advanced unresectable or metastatic gastrointestinal cancers of following histologies: * Colorectal adenocarcinoma * Gastric adenocarcinoma * Esophageal adenocarcinoma * Pancreatic adenocarcinoma * Cholangiocarcinoma and gallbladder carcinoma * Small intestine adenocarcinoma b. Phase Ib (expansion phase) * Histologically or cytologically confirmed, advanced unresectable or metastatic colorectal adenocarcinoma. * Patient who has failed all available conventional therapies known to confer clinical benefit for their disease based on local approved standards. For patients with colorectal cancer, prior treatment with regorafenib or TAS-102 is optional. * Phase Ia (dose escalation) only: Patient with either measurable or non-measurable/non-evaluable disease. * Phase Ia (expanded cohort) and Phase Ib (expansion phase) only: At least one target lesion that can be accurately measured per RECIST v.1.1 * Availability and willingness to provide an archived tumor tissue specimen and undergo tumor biopsy before treatment. Pre-treatment fresh tumor biopsy collections for biomarker analyses are considered optional in phase Ia and mandatory in phase Ib. Only nonsignificant risk procedures per the investigator's judgment will be used to obtain any biopsies specified in this study. In case a fresh tumor biopsy cannot be obtained due to before mentioned reasons an archived tumor tissue specimen obtained within ≤6 months of screening must be submitted. In case the patient undergoes baseline tumor biopsy, an archived tumor tissue specimen must be submitted regardless of the date of collection. * Adequate hepatic, renal and bone marrow functions as defined by all of the below: * Total bilirubin ≤ 1.5 x institutional Upper Level of Normal (ULN) (≤ 3 x institutional ULN for patient with Gilbert's syndrome) * ALT and AST ≤2.5 x institutional ULN (≤5 x institutional ULN for patients with known liver metastases) * Serum creatinine ≤1.5x institutional ULN. If creatinine is \> 1.5 x ULN, patient is eligible if concurrent creatinine clearance ≥ 50 ml/min (\>0.05 L/min) (measured or calculated by CKD-EPI formula or Japanese version of CKD-EPI formula for Japanese patients). * ANC ≥ 1.0x 10\^9/L (≥ 1.0 x 10\^3/μL, ≥ 1,000/mm3) * Platelets ≥ 100x10\^9/ L (≥ 100 x 10\^3/μL, ≥ 100 x 10\^3/mm3) * Hemoglobin (Hb) ≥8.5 g/dl, ≥ 85 g/L, or ≥ 5.3 mmol/L (without transfusion within previous week) * Serum lipase ≤ 1.5 institutional ULN * Recovery from any adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia CTCAE grade 2, sensory peripheral neuropathy CTCAE grade ≤ 2 or considered not clinically significant. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 * Life expectancy ≥ 3 months in the opinion of the investigator * Of legal adult age (according to local legislation) at screening * Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. * Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly.
Exclusion criteria
* Previous systemic anti-cancer therapy within the specified timeframe from the last dose intake to the first dose of trial treatment as shown below: * Any non-investigational drug, including anti-angiogenic antibodies (bevacizumab or ramucirumab) and anti-EGFR antibodies (cetuximab or panitumumab), within 14 days. * Any investigational drug or other antibodies including immune checkpoint inhibitors, within 28 days. * Radiation therapy within 4 weeks prior to start of treatment. However, palliative radiotherapy for symptomatic metastasis is allowed if completed within 2 weeks prior to start of treatment but must be discussed with the sponsor. * Any serious concomitant disease or medical condition affecting compliance with Trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal (GI) tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the Investigator, would make the patient inappropriate for entry into the trial. Any history of stroke or myocardial infarction within 6 months prior to screening. * Known pathological condition of GI tract, liver and pancreas, excluding the disease under study, that may interfere with assessment of drug safety or may increase the risk of toxicity: * inflammatory bowel disease * chronic pancreatitis * other serious GI pathological conditions by judgment of the investigator e.g. autoimmune disease with GI involvement, unexplained active diarrhea CTCAE grade ≥2 according to CTCAE v5.0. * Known history of human immunodeficiency virus infection. * Any of the following laboratory evidence of hepatitis virus infection. Test results obtained in routine diagnostics are acceptable if done within 14 days before the informed consent date: * Positive results of hepatitis B surface (HBs) antigen * Presence of HBc antibody together with HBV-DNA * Presence of hepatitis C RNA * Active concomitant malignancies, other than the one treated in this trial. * Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes the patient an unreliable trial participant or unlikely to comply with the protocol requirements or not expected to complete the trial as scheduled. * Women who are pregnant, nursing, or who plan to become pregnant while in the trial; female patients who do not agree to the interruption of breast feeding from the start of study treatment to within 30 days after the last study treatment. * Presence of uncontrolled or symptomatic brain or subdural metastases. Inclusion of patients with brain metastases who have completed local therapy and are considered stable by the investigator, or with newly identified asymptomatic brain metastases at screening will be allowed. Use of corticosteroids is allowed if the dose was stable for at least 1 week before the baseline MRI. * Patients who are under judicial protection and patients who are legally institutionalized * Major surgery (major according to the investigator's assessment) performed within 3 weeks prior to treatment start or planned within 3 months after screening, e.g. hip replacement. * Any of the following cardiac criteria: * Resting corrected QT interval (QTc) \>470 msec * Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block * Patients with an ejection fraction (EF) \<50% or the lower limit of normal of the institutional standard will be excluded. Only in cases where the Investigator (or the treating physician or both) suspects cardiac disease with negative effect on the EF, will the EF be measured during screening using an appropriate method according to local standards to confirm eligibility (e.g., echocardiogram, multi-gated acquisition scan). A historic measurement of EF no older than 6 months prior to first administration of study drug can be accepted provided that there is clinical evidence that the EF value has not worsened since this measurement in the opinion of the Investigator or of the treating physician or both. * Known hypersensitivity to the trial medication and/or its components i.e. polysorbate 20, sodium citrate, lysine hydrochloride, sucrose, citric acid.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of BI 905711 in Phase 1a | From cycle 1 Day 1 until the second administration of study treatment (two 14-day treatment cycles). | 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. |
| Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a | From cycle 1 Day 1 until the day before cycle 3 Day 1 (two 14-day treatment cycles). | Number of patients with dose-limiting toxicity (DLT) during the MTD evaluation period is reported. |
| Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined | 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. | 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. |
| Progression-free Survival (PFS) | From the first administration of trial medication until tumor progression or death, whichever occurred first, up to 48 weeks. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1b | 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. | Maximum measured plasma concentration (Cmax) of BI 905711 during the first cycle in phase 1b is reported. |
| Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1b | 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. | Maximum measured plasma concentration (Cmax) of BI 905711 during the third cycle in phase 1b is reported. |
| Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the First Cycle in Phase 1b | 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 is reported. 11. The AUC calculation includes an extrapolation from 168 hrs to 336 hrs to account for the weekly dosing schedule. |
| Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the Third Cycle in Phase 1b | 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 is reported. The AUC calculation includes an extrapolation from 168 hrs to 336 hrs to account for the weekly dosing schedule. |
| Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a | 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 first cycle in phase 1a is reported. |
| Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters | At baseline and every 8 weeks (± 7 days) until progression or start of further treatment for disease, up to 48 weeks. | 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. |
| Duration of Overall Response | 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. | 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. |
| Disease Control | 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. | 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. |
| Number of Patients With Treatment-emergent Adverse Events (AEs) | From start of treatment until the last dose of trial medication plus the residual effect period (REP), up to 358 days. | 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'. |
| Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a | 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 third cycle in phase 1a is reported. |
| Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the First Cycle in Phase 1a | 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 first cycle in phase 1a is reported. |
| Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the Third Cycle in Phase 1a | 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 third cycle in phase 1a is reported. |
Countries
Belgium, China, France, Germany, Japan, South Korea, Spain, United States
Participant flow
Recruitment details
The objectives of this phase 1a/b, open-label, multicenter, dose escalation and dose expansion trial were to explore safety and establish maximum tolerated dose (MTD) of BI 905711 in patients with gastrointestinal cancers, as well as to explore pharmacokinetics, pharmacodynamics, and efficacy. Recruitment for the trial was discontinued during Phase 1b and no PDAC (pancreatic ductal adenocarcinoma) patients were enrolled as originally planned.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| BI 905711 0.02 mg/kg, Q2W Patients with confirmed, advanced unresectable or metastatic gastrointestinal (GI) cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.02 milligram/kilogram (mg/kg) of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every two weeks. | 1 |
| BI 905711 0.06 mg/kg, Q2W Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.06 mg/kg of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every two weeks. | 1 |
| BI 905711 0.2 mg/kg, Q2W Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.2 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. | 7 |
| BI 905711 0.6 mg/kg, Q2W Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.6 mg/kg of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every two weeks. Participants in both the dose escalation and dose expansion phases at this dose were pooled together for baseline analysis. | 23 |
| BI 905711 0.6 mg/kg, QW Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.6 mg/kg of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every week for 3 weeks and then 1 week off (3 weeks on, 1 week off). | 16 |
| BI 905711 1.2 mg/kg, Q2W Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 1.2 mg/kg of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every two weeks. Participants in both the dose escalation and dose expansion phases at this dose were pooled together for baseline analysis. | 23 |
| BI 905711 2.4 mg/kg, Q2W Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 2.4 mg/kg of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every two weeks. Participants in both the dose escalation and dose expansion phases at this dose were pooled together for baseline analysis. | 24 |
| BI 905711 3.6 mg/kg, Q2W Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 3.6 mg/kg of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every two weeks. | 8 |
| BI 905711 4.8 mg/kg, Q2W Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 4.8 mg/kg of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every two weeks. | 7 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Clinical disease progression | 0 | 0 | 0 | 4 | 4 | 2 | 5 | 1 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lack of clinical benefit | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Objective disease progression | 1 | 1 | 6 | 18 | 12 | 20 | 18 | 7 | 6 |
Baseline characteristics
| Characteristic | Total | BI 905711 0.06 mg/kg, Q2W | BI 905711 0.2 mg/kg, Q2W | BI 905711 0.6 mg/kg, Q2W | BI 905711 0.6 mg/kg, QW | BI 905711 0.02 mg/kg, Q2W | BI 905711 1.2 mg/kg, Q2W | BI 905711 2.4 mg/kg, Q2W | BI 905711 3.6 mg/kg, Q2W | BI 905711 4.8 mg/kg, Q2W |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.8 Years STANDARD_DEVIATION 10.4 | 71.0 Years | 64.3 Years STANDARD_DEVIATION 6.7 | 56.0 Years STANDARD_DEVIATION 10.1 | 57.3 Years STANDARD_DEVIATION 10.5 | 59.0 Years | 57.7 Years STANDARD_DEVIATION 11.5 | 63.0 Years STANDARD_DEVIATION 10.9 | 64.9 Years STANDARD_DEVIATION 7 | 62.4 Years STANDARD_DEVIATION 6.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants | 1 Participants | 7 Participants | 19 Participants | 14 Participants | 1 Participants | 18 Participants | 19 Participants | 8 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 80 Participants | 0 Participants | 5 Participants | 17 Participants | 13 Participants | 0 Participants | 18 Participants | 18 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Female | 47 Participants | 0 Participants | 1 Participants | 9 Participants | 7 Participants | 0 Participants | 16 Participants | 10 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 63 Participants | 1 Participants | 6 Participants | 14 Participants | 9 Participants | 1 Participants | 7 Participants | 14 Participants | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 1 / 1 | 5 / 7 | 15 / 23 | 6 / 16 | 15 / 23 | 11 / 24 | 7 / 8 | 4 / 7 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 5 / 7 | 22 / 23 | 16 / 16 | 23 / 23 | 19 / 24 | 7 / 8 | 7 / 7 |
| serious Total, serious adverse events | 0 / 1 | 1 / 1 | 2 / 7 | 14 / 23 | 4 / 16 | 7 / 23 | 10 / 24 | 2 / 8 | 1 / 7 |
Outcome results
Primary
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.
Population: Treated set (TS): This included all subjects who were dispensed study medication and were documented to have been treated with at least one dose of BI 905711. The TS was used for both safety and efficacy analyses. While the protocol specified endpoints separately for Phase 1a/1b, final analysis of most endpoints (except pharmacokinetic and MTD endpoints) were based on the Treated set, with Phase 1a and 1b patients pooled, as seen here. Only participants with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined | 0 Participants |
| BI 905711 0.06 mg/kg, Q2W | Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined | 0 Participants |
| BI 905711 0.2 mg/kg, Q2W | Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined | 0 Participants |
| BI 905711 0.6 mg/kg, Q2W | Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined | 0 Participants |
| BI 905711 1.2 mg/kg, Q2W | Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined | 0 Participants |
| BI 905711 2.4 mg/kg, Q2W | Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined | 0 Participants |
| BI 905711 3.6 mg/kg, Q2W | Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined | 0 Participants |
| BI 905711 4.8 mg/kg, Q2W | Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined | 0 Participants |
| BI 905711 4.8 mg/kg, Q2W | Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined | 0 Participants |
Primary
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).
Population: MTD evaluation set (MTDS): This included all patients in the treated set (TS) who were not replaced for the MTD determination. The MTDS was used for the primary analyses of drug limiting-toxicities (DLTs) and MTD determination. This analysis was carried out for participants in the Phase 1a part of trial.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Maximum Tolerated Dose (MTD) of BI 905711 in Phase 1a | NA milligram / kilogram (mg/kg) |
Primary
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).
Population: MTD evaluation set (MTDS): This included all patients in the treated set (TS) who were not replaced for the MTD determination. The MTDS was used for the primary analyses of drug limiting-toxicities (DLTs) and MTD determination in Phase 1a.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a | 0 Participants |
| BI 905711 0.06 mg/kg, Q2W | Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a | 0 Participants |
| BI 905711 0.2 mg/kg, Q2W | Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a | 0 Participants |
| BI 905711 0.6 mg/kg, Q2W | Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a | 0 Participants |
| BI 905711 1.2 mg/kg, Q2W | Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a | 0 Participants |
| BI 905711 2.4 mg/kg, Q2W | Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a | 0 Participants |
| BI 905711 3.6 mg/kg, Q2W | Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a | 0 Participants |
| BI 905711 4.8 mg/kg, Q2W | Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a | 0 Participants |
Primary
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.
Population: Treated set (TS): This included all subjects who were dispensed study medication and were documented to have been treated with at least one dose of BI 905711. This TS was used for both safety and efficacy analyses. Only participants with data were included in analysis and final analysis of PFS was based on the TS, with Phase 1a and Phase 1b patients pooled.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Progression-free Survival (PFS) | 6.29 weeks |
| BI 905711 0.06 mg/kg, Q2W | Progression-free Survival (PFS) | 18.14 weeks |
| BI 905711 0.2 mg/kg, Q2W | Progression-free Survival (PFS) | 5.71 weeks |
| BI 905711 0.6 mg/kg, Q2W | Progression-free Survival (PFS) | 7.36 weeks |
| BI 905711 1.2 mg/kg, Q2W | Progression-free Survival (PFS) | 7.43 weeks |
| BI 905711 2.4 mg/kg, Q2W | Progression-free Survival (PFS) | 6.14 weeks |
| BI 905711 3.6 mg/kg, Q2W | Progression-free Survival (PFS) | 7.14 weeks |
| BI 905711 4.8 mg/kg, Q2W | Progression-free Survival (PFS) | 11.43 weeks |
| BI 905711 4.8 mg/kg, Q2W | Progression-free Survival (PFS) | 7.43 weeks |
Secondary
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.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This included all subjects in the treated set (TS) who provided at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with available data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the First Cycle in Phase 1b | 323000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 48 |
| BI 905711 0.06 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the First Cycle in Phase 1b | 302000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 40.6 |
| BI 905711 0.2 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the First Cycle in Phase 1b | 573000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 55.3 |
| BI 905711 0.6 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the First Cycle in Phase 1b | 1460000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 50 |
Secondary
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.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This included all subjects in the treated set (TS) who provided at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with available data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the Third Cycle in Phase 1b | 354000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 42.9 |
| BI 905711 0.06 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the Third Cycle in Phase 1b | 339000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 48.1 |
| BI 905711 0.2 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the Third Cycle in Phase 1b | 571000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 78.9 |
| BI 905711 0.6 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the Third Cycle in Phase 1b | 1460000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 55.9 |
Secondary
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 .
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This included all subjects in the treated set (TS) who provided at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Due to premature discontinuation of the trial, no additional patients with pancreatic ductal adenocarcinoma were recruited. Only participants with available data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 905711 0.06 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the First Cycle in Phase 1a | 20000 hour*nanogram/milliliter (h*ng/mL) | — |
| BI 905711 0.2 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the First Cycle in Phase 1a | 97500 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 39.5 |
| BI 905711 0.6 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the First Cycle in Phase 1a | 391000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 50.1 |
| BI 905711 1.2 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the First Cycle in Phase 1a | 872000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 39.8 |
| BI 905711 2.4 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the First Cycle in Phase 1a | 1770000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 52 |
| BI 905711 3.6 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the First Cycle in Phase 1a | 3330000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 22.3 |
| BI 905711 4.8 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the First Cycle in Phase 1a | 4590000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 29.8 |
Secondary
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.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This included all subjects in the treated set (TS) who provided at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Due to premature discontinuation of the trial, no additional patients with pancreatic ductal adenocarcinoma were recruited.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 905711 0.06 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the Third Cycle in Phase 1a | 24500 hour*nanogram/milliliter (h*ng/mL) | — |
| BI 905711 0.2 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the Third Cycle in Phase 1a | 104000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 26.8 |
| BI 905711 0.6 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the Third Cycle in Phase 1a | 358000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 37.2 |
| BI 905711 1.2 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the Third Cycle in Phase 1a | 717000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 21.3 |
| BI 905711 2.4 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the Third Cycle in Phase 1a | 1990000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 76.3 |
| BI 905711 3.6 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the Third Cycle in Phase 1a | 3390000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 41.2 |
| BI 905711 4.8 mg/kg, Q2W | Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the Third Cycle in Phase 1a | 3990000 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 63.3 |
Secondary
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.
Population: Treated set (TS): This included all subjects who were dispensed study medication and were documented to have been treated with at least one dose of BI 905711. This TS was used for both safety and efficacy analyses. Only participants with data were included in the analysis and final analysis of patients was based on the TS, with phase 1a and phase 1b patients pooled.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Disease Control | 0 Participants |
| BI 905711 0.06 mg/kg, Q2W | Disease Control | 1 Participants |
| BI 905711 0.2 mg/kg, Q2W | Disease Control | 0 Participants |
| BI 905711 0.6 mg/kg, Q2W | Disease Control | 7 Participants |
| BI 905711 1.2 mg/kg, Q2W | Disease Control | 2 Participants |
| BI 905711 2.4 mg/kg, Q2W | Disease Control | 2 Participants |
| BI 905711 3.6 mg/kg, Q2W | Disease Control | 6 Participants |
| BI 905711 4.8 mg/kg, Q2W | Disease Control | 4 Participants |
| BI 905711 4.8 mg/kg, Q2W | Disease Control | 1 Participants |
Secondary
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.
Population: Treated set (TS): This included all subjects who were dispensed study medication and were documented to have been treated with at least one dose of BI 905711. This TS was used for both safety and efficacy analyses. Only participants with data were included in analysis and final analysis of overall response was based on the TS, with phase 1a and phase 1b patients pooled.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 905711 0.06 mg/kg, Q2W | Duration of Overall Response | 127.0 Days | — |
| BI 905711 0.6 mg/kg, Q2W | Duration of Overall Response | 170.3 Days | Standard Deviation 84.5 |
| BI 905711 1.2 mg/kg, Q2W | Duration of Overall Response | 196.5 Days | Standard Deviation 119.5 |
| BI 905711 2.4 mg/kg, Q2W | Duration of Overall Response | 87.0 Days | Standard Deviation 58 |
| BI 905711 3.6 mg/kg, Q2W | Duration of Overall Response | 190.7 Days | Standard Deviation 78.7 |
| BI 905711 4.8 mg/kg, Q2W | Duration of Overall Response | 90.5 Days | Standard Deviation 45.5 |
| BI 905711 4.8 mg/kg, Q2W | Duration of Overall Response | 260.0 Days | — |
Secondary
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.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This included all subjects in the treated set (TS) who provided at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Participants in the Phase 1a part were analyzed for this endpoint.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a | 306 nanograms/milliliter (ng/ml) | — |
| BI 905711 0.06 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a | 492 nanograms/milliliter (ng/ml) | — |
| BI 905711 0.2 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a | 2110 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 16.1 |
| BI 905711 0.6 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a | 6690 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 18.4 |
| BI 905711 1.2 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a | 11900 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 29.5 |
| BI 905711 2.4 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a | 26200 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 24.3 |
| BI 905711 3.6 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a | 40700 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 22.5 |
| BI 905711 4.8 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a | 61000 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 26.9 |
Secondary
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.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This included all subjects in the treated set (TS) who provided at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1b | 5740 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 31 |
| BI 905711 0.06 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1b | 6150 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 31 |
| BI 905711 0.2 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1b | 10700 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 36.7 |
| BI 905711 0.6 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1b | 23100 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 26.6 |
Secondary
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.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This included all subjects in the treated set (TS) who provided at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with available data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a | 336 nanograms/milliliter (ng/ml) | — |
| BI 905711 0.06 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a | 497 nanograms/milliliter (ng/ml) | — |
| BI 905711 0.2 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a | 2580 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 17.5 |
| BI 905711 0.6 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a | 7030 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 20.9 |
| BI 905711 1.2 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a | 10300 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 44.8 |
| BI 905711 2.4 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a | 31900 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 26.4 |
| BI 905711 3.6 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a | 47700 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 23.9 |
| BI 905711 4.8 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a | 50300 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 32.1 |
Secondary
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.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This included all subjects in the treated set (TS) who provided at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with available data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1b | 5630 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 28 |
| BI 905711 0.06 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1b | 6310 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 47.8 |
| BI 905711 0.2 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1b | 13600 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 39.5 |
| BI 905711 0.6 mg/kg, Q2W | Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1b | 23100 nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 20.9 |
Secondary
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.
Population: Treated set (TS): This included all subjects who were dispensed study medication and were documented to have been treated with at least one dose of BI 905711. This TS was used for both safety and efficacy analyses. Only participants with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters | 13.6 Percentage change in tumor diameter | — |
| BI 905711 0.06 mg/kg, Q2W | Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters | -2.4 Percentage change in tumor diameter | — |
| BI 905711 0.2 mg/kg, Q2W | Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters | 28.8 Percentage change in tumor diameter | Standard Deviation 13.85 |
| BI 905711 0.6 mg/kg, Q2W | Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters | 20.8 Percentage change in tumor diameter | Standard Deviation 28.86 |
| BI 905711 1.2 mg/kg, Q2W | Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters | 26.6 Percentage change in tumor diameter | Standard Deviation 26.43 |
| BI 905711 2.4 mg/kg, Q2W | Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters | 34.3 Percentage change in tumor diameter | Standard Deviation 24.76 |
| BI 905711 3.6 mg/kg, Q2W | Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters | 18.2 Percentage change in tumor diameter | Standard Deviation 25.9 |
| BI 905711 4.8 mg/kg, Q2W | Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters | 19.3 Percentage change in tumor diameter | Standard Deviation 20.93 |
| BI 905711 4.8 mg/kg, Q2W | Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters | 26.8 Percentage change in tumor diameter | Standard Deviation 23.02 |
Secondary
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.
Population: Treated set (TS): This included all subjects who were dispensed study medication and were documented to have been treated with at least one dose of BI 905711. This TS was used for both safety and efficacy analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 905711 0.02mg/kg - 4.8 mg/kg, Q2W | Number of Patients With Treatment-emergent Adverse Events (AEs) | 1 Participants |
| BI 905711 0.06 mg/kg, Q2W | Number of Patients With Treatment-emergent Adverse Events (AEs) | 1 Participants |
| BI 905711 0.2 mg/kg, Q2W | Number of Patients With Treatment-emergent Adverse Events (AEs) | 5 Participants |
| BI 905711 0.6 mg/kg, Q2W | Number of Patients With Treatment-emergent Adverse Events (AEs) | 22 Participants |
| BI 905711 1.2 mg/kg, Q2W | Number of Patients With Treatment-emergent Adverse Events (AEs) | 16 Participants |
| BI 905711 2.4 mg/kg, Q2W | Number of Patients With Treatment-emergent Adverse Events (AEs) | 23 Participants |
| BI 905711 3.6 mg/kg, Q2W | Number of Patients With Treatment-emergent Adverse Events (AEs) | 20 Participants |
| BI 905711 4.8 mg/kg, Q2W | Number of Patients With Treatment-emergent Adverse Events (AEs) | 8 Participants |
| BI 905711 4.8 mg/kg, Q2W | Number of Patients With Treatment-emergent Adverse Events (AEs) | 7 Participants |