Multiple Myeloma
Conditions
Brief summary
The primary objective of this trial is to determine the maximum tolerated dose (MTD) of BI 836909 administered by continuous i.v. infusion in patients with relapsed and/or refractory multiple myeloma. If the MTD is not reached based on safety findings, a recommended dose for further development will be determined. This will depend on the safety data, pharmacokinetic/pharmacodynamics data and potentially preliminary efficacy data. Secondary objectives are to document the safety and tolerability of BI 836909, to perform pharmacokinetic and pharmacodynamic analyses and to evaluate relevant biological effects in terms of parameters of efficacy.
Interventions
DRUGBI 836909
Intravenous Infusion of BI 836909.
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Patients with a documented diagnosis of relapsed and/or refractory multiple myeloma who progressed after at least two prior treatment regimens, including both proteasome inhibitor as well as an immune-modulatory drug at time of screening * must have measurable disease, defined by one or more of following at time of screening: * a serum M protein \> 0.5 g/dl measured by serum protein electrophoresis * urinary M protein excretion \> 200 mg/24 hours * serum free light chain (FLC) measurement \> 10 mg/dl, provided that the serum FLC ratio is abnormal * Relapse or progression of disease with an indication for therapy as per investigator´s judgement at time of screening * ECOG Performance Status 0, 1 or 2 at time of screening * Age \>= 18 years at time of screening * Written informed consent which is consistent with ICH\_GCP guidelines and local legislation * Able to adhere to the study visit schedule e.g. ability to come to the clinic and to other protocol requirements * Indwelling central venous catheter or willingness to undergo intra venous central line placement.
Exclusion criteria
* Plasma cell leukemia * Extramedullary relapse of multiple myeloma * Known central nervous system involvement by multiple myeloma * Last anticancer treatment \< 2 weeks prior to visit 1 * Last treatment with a therapeutic antibody less than 6 weeks prior to visit 1 * Prior allogeneic stem cell transplantation or solid organ transplantation * Autologous bone marrow transplantation \< than 90 days at time of treatment start * Last corticosteroid \< 2 weeks prior to visit 1 unless the dose is \<= 10 mg/day prednisolone or equivalent * AST or ALT \> 3 x upper limit of normal (CTCAE version 4.03 grade 2 or higher) at time of screening * Total conjugated bilirubin \> 1.5 x upper limit of normal (CTCAE version 4.03 grade 2 or higher) at time of screening * Absolute neutrophil count \< 1.0 x 109/L (without growth factor support) at time of screening * Platelets \< 25 x 109/L (without transfusions) at time of screening * Calculated GFR \< 30 mL/min (Cockcroft-Gault Formula) at time of screening * Clinical relevant concurrent medical disease or condition which according to the investigator's judgement would either compromise patient safety or interfere with the evaluation of the safety of the test drug, e.g. symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring therapy at time of screening * clinically not controlled chronic or ongoing infectious disease requiring treatment at the time of enrolment or within the previous two weeks * Active hepatitis B or C, or laboratory evidence for a chronic infection with hepatitis B or C at time of screening; HIV infection at time of screening * Women of childbearing potential not using highly effective method of birth control during the trial until one year after the last dose. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year)when used consistently and correctly used such as implants, injectables, combined oral contraceptives, intrauterine devises (IUDs), sexual abstinence or vasectomised partner. Barrier methods of contraception are accepted if condom or occlusive cap is used together with spermicides (e.g. foam, gel). Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or postmenopausal (12 months with no menses without an alternative medical cause * Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the trial and for a minimum of 6 months after treatment * Pregnancy or breast feeding * Known or suspected active alcohol or drug abuse as per investigator's judgement * Treatment with another investigational drug within the past four weeks before start of therapy or concomitantly with this trial * Patients with known hypersensitivity to any component of the study drug * Patients with other malignancies within 5 years at time of screening (except basal cell or squamous cell carcinoma of the skin or carcinoma in situ treated with curative therapy) * Known autoimmune diseases requiring systemic treatment in past 5 years and interfering with evaluation of study drug * Pre-existing disorders of the central nervous system
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Maximum Tolerated Dose (MTD) of BI 836909 | Cycle 1, up to 6 weeks. | The Maximum tolerated dose (MTD) of BI 836909, which was defined as the highest dose of the dose level tested where ≤1 patient out of 6 developed a Dose-limiting toxicity (DLT). The MTD was defined based on DLTs observed during Cycle 1. However, all Adverse Events corresponding to the definition of a DLT (see below) were to be considered for confirming the MTD. A DLT was defined as any drug-related non-haematological Adverse Event of Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher. |
| The Number of Patients With Dose-limiting Toxicities (DLTs) | Cycle 1, up to 6 weeks. | The number of patients with Dose-limiting toxicities (DLTs) in cycle 1. A Dose-limiting toxicity was defined as any drug-related non-haematological Adverse Event of Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Objective Response - Including Extended Follow up Visits | From start of treatment till the last extended follow-up visit which is scheduled at 12 months after end of treatment, up to 113 weeks. | For patients with objective response, the duration of response was calculated from the time of first recorded achievement of a response (sCR, CR, PR, or VGPR) until documented progression or death. The Kaplan-Meier method was used to calculate the estimates. |
| Number of Participants With a Minimal Residual Disease (MRD) Response | On-treatment: From start of treatment till end of trial (EOT) visit, up to 61 weeks. Follow-up: From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks. | Minimal residual disease (MRD) response was defined as \<1 tumour cell within 10000 normal cells in bone marrow. MRD was determined using Fluorescence-activated cell sorting (FACS) analysis. |
| Duration of Minimal Residual Disease (MRD) Response - on Treatment | From start of treatment till end of trial (EOT) visit, up to 61 weeks. | Duration of MRD response was calculated from the time of first recorded achievement of a MRD response to documented progression or death. The Kaplan-Meier method was used to calculate the estimates. |
| Number of Participants With an Objective Response | On-treatment: From start of treatment till end of trial (EOT) visit, up to 61 weeks. Extended follow-up: From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks. | Objective responses: Stringent complete response (sCR): CR + normal Free light chain (FLC) ratio and no clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow. Very good partial response (VGPR): serum and urine M protein detectable by immunofixation but not on electrophoresis or \>90% reduction in serum M protein plus urine M protein level \<100 mg/24h. PR: \>50% reduction of serum and 24 h urinary M protein by \>90% or to \<200mg/24h. If unmeasurable, a \>50% decrease in difference between involved and uninvolved FLC levels instead of M protein criteria. if FLC assay was not measurable, a \>50% reduction in plasma cells was required instead of M protein, provided baseline bone marrow plasma cell was \>30%. In addition to the listed criteria, a \>50% reduction in the size of soft tissue plasmacytomas was also required, if present at baseline. |
| Progression-free Survival (PFS) - on Treatment | From start of treatment till end of trial (EOT) visit, up to 61 weeks. | PFS was defined as time from first treatment with BI 836909 till disease progression or death. Progression was defined according to International Myeloma Working Group (IMWG 2006) response criteria as an increase \>25% from lowest response value in any of the following parameters: -Serum M protein (absolute increase had to be \>0.5 gram/ deciliters (dL)) -Urine M protein (absolute increase had to be \>200 milligram (mg)/24 hour) -Only in patients without measurable serum and urine M protein levels The difference between involved and uninvolved FLC levels. Absolute increase had to be \>10 mg/dL -Bone marrow plasma cell percentage; absolute percentage had to be \>10% -Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas -Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 Millimole/Liter) that was attributed solely to the plasma cell proliferative disorder. |
| Progression-free Survival (PFS) - Including Extended Follow up Visits | From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks. | PFS was defined as time from first treatment with BI 836909 till disease progression or death. Progression was defined according to International Myeloma Working Group (IMWG 2006) response criteria as an increase \>25% from lowest response value in any of the following parameters: -Serum M protein (absolute increase had to be \>0.5 gram/ deciliters (dL)) -Urine M protein (absolute increase had to be \>200 milligram (mg)/24 hour) -Only in patients without measurable serum and urine M protein levels The difference between involved and uninvolved FLC levels. Absolute increase had to be \>10 mg/dL -Bone marrow plasma cell percentage; absolute percentage had to be \>10% -Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas -Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 Millimole/Liter) that was attributed solely to the plasma cell proliferative disorder |
| Serum Concentration at Steady State of BI 836909 (Css) | Pharmacokinetic samples were collected at 48:00 hours (h):minutes (min), 168:00, 336:00, 504:00 and 671:50 h after the start of infusion of BI 836909 of the first cycle. | Serum concentration at steady state of BI 836909 (Css). |
| Duration of Minimal Residual Disease (MRD) Response - Including Extended Follow up Visits | From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks. | Duration of MRD response was calculated from the time of first recorded achievement of a MRD response to documented progression or death. The Kaplan-Meier method was used to calculate the estimates. |
| Duration of Objective Response - on Treatment | From start of treatment till end of trial (EOT) visit, up to 61 weeks. | For patients with objective response, the duration of response was calculated from the time of first recorded achievement of a response (sCR, CR, PR, or VGPR) until documented progression or death. The Kaplan-Meier method was used to calculate the estimates. |
Countries
France, Germany
Participant flow
Recruitment details
This was an open-label, non-randomised, phase I, dose escalation trial in patients with relapsed and/or refractory multiple myeloma. The first 4 dose levels (0.2, 0.4,0.8, and 1.6 Microgram Per Day (μg/d)) were tested in single patient cohorts. Dose levels ≥3.2 μg/d (3.2, 6.5, 13, 25, 50, 100, 200, 400, and 800 μg/d) were to be tested in a 3+3 design. Once the Maximum tolerated dose (MTD) was determined, up to 6 additional patients were to be treated at the MTD or at the recommended dose.
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 |
|---|---|
| Intravenous Infusion of BI 836909 (Overall in the 4 Lowest Dose Cohorts 0.2, 0.4, 0.8, 1.6 μg/d) Intravenous infusion of BI 836909 (overall in the 4 lowest dose cohorts 0.2, 0.4, 0.8, 1.6 microgram per day (μg/d)). BI 836909 was administered as 4-week continuous intravenous infusion (c.i.v.) followed by a 2-week treatment break for 5 cycles or until progression, unacceptable adverse events, or any other reason necessitating withdrawal. In case of ongoing clinical benefit and if considered indicated by the investigator, 5 additional treatment cycles could be done, leading to a maximum of 10 cycles. | 5 |
| Intravenous Infusion of BI 836909 (3.2 μg/d) Intravenous infusion of BI 836909 (3.2 microgram per day (μg/d)). BI 836909 was administered as 4-week continuous intravenous infusion (c.i.v.) followed by a 2-week treatment break for 5 cycles or until progression, unacceptable adverse events, or any other reason necessitating withdrawal. In case of ongoing clinical benefit and if considered indicated by the investigator, 5 additional treatment cycles could be done, leading to a maximum of 10 cycles. | 3 |
| Intravenous Infusion of BI 836909 (6.5 μg/d) Intravenous infusion of BI 836909 (6.5 microgram per day (μg/d)). BI 836909 was administered as 4-week continuous intravenous infusion (c.i.v.) followed by a 2-week treatment break for 5 cycles or until progression, unacceptable adverse events, or any other reason necessitating withdrawal. In case of ongoing clinical benefit and if considered indicated by the investigator, 5 additional treatment cycles could be done, leading to a maximum of 10 cycles. | 3 |
| Intravenous Infusion of BI 836909 (13 μg/d) Intravenous infusion of BI 836909 (13 microgram per day (μg/d)). BI 836909 was administered as 4-week continuous intravenous infusion (c.i.v.) followed by a 2-week treatment break for 5 cycles or until progression, unacceptable adverse events, or any other reason necessitating withdrawal. In case of ongoing clinical benefit and if considered indicated by the investigator, 5 additional treatment cycles could be done, leading to a maximum of 10 cycles. | 3 |
| Intravenous Infusion of BI 836909 (25 μg/d) Intravenous infusion of BI 836909 (25 microgram per day (μg/d)). BI 836909 was administered as 4-week continuous intravenous infusion (c.i.v.) followed by a 2-week treatment break for 5 cycles or until progression, unacceptable adverse events, or any other reason necessitating withdrawal. In case of ongoing clinical benefit and if considered indicated by the investigator, 5 additional treatment cycles could be done, leading to a maximum of 10 cycles. | 3 |
| Intravenous Infusion of BI 836909 (50 μg/d) Intravenous infusion of BI 836909 (50 microgram per day (μg/d)). BI 836909 was administered as 4-week continuous intravenous infusion (c.i.v.) followed by a 2-week treatment break for 5 cycles or until progression, unacceptable adverse events, or any other reason necessitating withdrawal. In case of ongoing clinical benefit and if considered indicated by the investigator, 5 additional treatment cycles could be done, leading to a maximum of 10 cycles. | 5 |
| Intravenous Infusion of BI 836909 (100 μg/d) Intravenous infusion of BI 836909 (100 microgram per day (μg/d)). BI 836909 was administered as 4-week continuous intravenous infusion (c.i.v.) followed by a 2-week treatment break for 5 cycles or until progression, unacceptable adverse events, or any other reason necessitating withdrawal. In case of ongoing clinical benefit and if considered indicated by the investigator, 5 additional treatment cycles could be done, leading to a maximum of 10 cycles. | 4 |
| Intravenous Infusion of BI 836909 (200 μg/d) Intravenous infusion of BI 836909 (200 microgram per day (μg/d)). BI 836909 was administered as 4-week continuous intravenous infusion (c.i.v.) followed by a 2-week treatment break for 5 cycles or until progression, unacceptable adverse events, or any other reason necessitating withdrawal. In case of ongoing clinical benefit and if considered indicated by the investigator, 5 additional treatment cycles could be done, leading to a maximum of 10 cycles. | 3 |
| Intravenous Infusion of BI 836909 (400 μg/d) Intravenous infusion of BI 836909 (400 microgram per day (μg/d)). BI 836909 was administered as 4-week continuous intravenous infusion (c.i.v.) followed by a 2-week treatment break for 5 cycles or until progression, unacceptable adverse events, or any other reason necessitating withdrawal. In case of ongoing clinical benefit and if considered indicated by the investigator, 5 additional treatment cycles could be done, leading to a maximum of 10 cycles. | 10 |
| Intravenous Infusion of BI 836909 (800 μg/d) Intravenous infusion of BI 836909 (800 microgram per day (μg/d)). BI 836909 was administered as 4-week continuous intravenous infusion (c.i.v.) followed by a 2-week treatment break for 5 cycles or until progression, unacceptable adverse events, or any other reason necessitating withdrawal. In case of ongoing clinical benefit and if considered indicated by the investigator, 5 additional treatment cycles could be done, leading to a maximum of 10 cycles. | 3 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Dose-limiting toxicity (DLT) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 |
| Overall Study | Not treated | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other Adverse Events | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 2 | 0 |
| Overall Study | Progressive disease | 3 | 3 | 2 | 2 | 3 | 3 | 4 | 2 | 5 | 0 |
| Overall Study | Refused to continue trial medication | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Intravenous Infusion of BI 836909 (Overall in the 4 Lowest Dose Cohorts 0.2, 0.4, 0.8, 1.6 μg/d) | Intravenous Infusion of BI 836909 (3.2 μg/d) | Intravenous Infusion of BI 836909 (6.5 μg/d) | Intravenous Infusion of BI 836909 (13 μg/d) | Intravenous Infusion of BI 836909 (25 μg/d) | Intravenous Infusion of BI 836909 (50 μg/d) | Intravenous Infusion of BI 836909 (100 μg/d) | Intravenous Infusion of BI 836909 (200 μg/d) | Intravenous Infusion of BI 836909 (400 μg/d) | Intravenous Infusion of BI 836909 (800 μg/d) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 9.9 | 58.6 years STANDARD_DEVIATION 12.3 | 67.7 years STANDARD_DEVIATION 2.5 | 63.0 years STANDARD_DEVIATION 9.8 | 69.3 years STANDARD_DEVIATION 6.1 | 67.0 years STANDARD_DEVIATION 7.5 | 61.6 years STANDARD_DEVIATION 4.6 | 62.5 years STANDARD_DEVIATION 7.8 | 62.7 years STANDARD_DEVIATION 14.5 | 57.7 years STANDARD_DEVIATION 12.2 | 71.3 years STANDARD_DEVIATION 8.6 |
| 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 | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 28 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 8 Participants | 2 Participants |
| Sex: Female, Male Female | 15 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 27 Participants | 4 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 7 Participants | 0 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 | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 2 | 0 / 1 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 1 / 5 | 0 / 4 | 0 / 3 | 1 / 10 | 0 / 3 | 2 / 42 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 2 | 1 / 1 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 5 / 5 | 4 / 4 | 3 / 3 | 10 / 10 | 2 / 3 | 40 / 42 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 | 1 / 2 | 0 / 1 | 1 / 3 | 3 / 3 | 1 / 3 | 1 / 3 | 3 / 5 | 2 / 4 | 3 / 3 | 8 / 10 | 3 / 3 | 27 / 42 |
Outcome results
Primary
The Maximum Tolerated Dose (MTD) of BI 836909
The Maximum tolerated dose (MTD) of BI 836909, which was defined as the highest dose of the dose level tested where ≤1 patient out of 6 developed a Dose-limiting toxicity (DLT). The MTD was defined based on DLTs observed during Cycle 1. However, all Adverse Events corresponding to the definition of a DLT (see below) were to be considered for confirming the MTD. A DLT was defined as any drug-related non-haematological Adverse Event of Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher.
Time frame: Cycle 1, up to 6 weeks.
Population: MTD evaluation set (MTDS): all patients who were administered trial medication and who were not replaced for the Maximum tolerated dose (MTD) determination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | The Maximum Tolerated Dose (MTD) of BI 836909 | 400 Microgram Per Day (μg/d) |
Primary
The Number of Patients With Dose-limiting Toxicities (DLTs)
The number of patients with Dose-limiting toxicities (DLTs) in cycle 1. A Dose-limiting toxicity was defined as any drug-related non-haematological Adverse Event of Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher.
Time frame: Cycle 1, up to 6 weeks.
Population: MTD evaluation set (MTDS): all patients who were administered trial medication and who were not replaced for the Maximum tolerated dose (MTD) determination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | The Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | The Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | The Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | The Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | The Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | The Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | The Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | The Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | The Number of Patients With Dose-limiting Toxicities (DLTs) | 1 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | The Number of Patients With Dose-limiting Toxicities (DLTs) | 2 Participants |
Secondary
Duration of Minimal Residual Disease (MRD) Response - Including Extended Follow up Visits
Duration of MRD response was calculated from the time of first recorded achievement of a MRD response to documented progression or death. The Kaplan-Meier method was used to calculate the estimates.
Time frame: From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks.
Population: All patients who were administered trial medication and showed a Minimal residual disease (MRD) response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Duration of Minimal Residual Disease (MRD) Response - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (200 μg/d) | Duration of Minimal Residual Disease (MRD) Response - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (400 μg/d) | Duration of Minimal Residual Disease (MRD) Response - Including Extended Follow up Visits | 20.70 Months |
Secondary
Duration of Minimal Residual Disease (MRD) Response - on Treatment
Duration of MRD response was calculated from the time of first recorded achievement of a MRD response to documented progression or death. The Kaplan-Meier method was used to calculate the estimates.
Time frame: From start of treatment till end of trial (EOT) visit, up to 61 weeks.
Population: All patients who were administered trial medication and showed a Minimal residual disease (MRD) response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Duration of Minimal Residual Disease (MRD) Response - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (200 μg/d) | Duration of Minimal Residual Disease (MRD) Response - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (400 μg/d) | Duration of Minimal Residual Disease (MRD) Response - on Treatment | NA Months |
Secondary
Duration of Objective Response - Including Extended Follow up Visits
For patients with objective response, the duration of response was calculated from the time of first recorded achievement of a response (sCR, CR, PR, or VGPR) until documented progression or death. The Kaplan-Meier method was used to calculate the estimates.
Time frame: From start of treatment till the last extended follow-up visit which is scheduled at 12 months after end of treatment, up to 113 weeks.
Population: All patients who were administered trial medication and showed an objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Duration of Objective Response - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (50 μg/d) | Duration of Objective Response - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (100 μg/d) | Duration of Objective Response - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (200 μg/d) | Duration of Objective Response - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (400 μg/d) | Duration of Objective Response - Including Extended Follow up Visits | 23.62 Months |
| Intravenous Infusion of BI 836909 (800 μg/d) | Duration of Objective Response - Including Extended Follow up Visits | NA Months |
Secondary
Duration of Objective Response - on Treatment
For patients with objective response, the duration of response was calculated from the time of first recorded achievement of a response (sCR, CR, PR, or VGPR) until documented progression or death. The Kaplan-Meier method was used to calculate the estimates.
Time frame: From start of treatment till end of trial (EOT) visit, up to 61 weeks.
Population: All patients who were administered trial medication and showed an objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Duration of Objective Response - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (50 μg/d) | Duration of Objective Response - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (100 μg/d) | Duration of Objective Response - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (200 μg/d) | Duration of Objective Response - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (400 μg/d) | Duration of Objective Response - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (800 μg/d) | Duration of Objective Response - on Treatment | NA Months |
Secondary
Number of Participants With a Minimal Residual Disease (MRD) Response
Minimal residual disease (MRD) response was defined as \<1 tumour cell within 10000 normal cells in bone marrow. MRD was determined using Fluorescence-activated cell sorting (FACS) analysis.
Time frame: On-treatment: From start of treatment till end of trial (EOT) visit, up to 61 weeks. Follow-up: From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks.
Population: Treated set (TS): all patients who were administered trial medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment | 0 Participants |
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment + extended follow-up visits (follow-up) | 0 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment | 0 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment + extended follow-up visits (follow-up) | 0 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment | 1 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment + extended follow-up visits (follow-up) | 1 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment | 0 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment + extended follow-up visits (follow-up) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment + extended follow-up visits (follow-up) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment | 0 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment + extended follow-up visits (follow-up) | 0 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment | 0 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment + extended follow-up visits (follow-up) | 0 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment | 0 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment | 1 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment + extended follow-up visits (follow-up) | 1 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment | 6 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment + extended follow-up visits (follow-up) | 6 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment | 0 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With a Minimal Residual Disease (MRD) Response | On treatment + extended follow-up visits (follow-up) | 0 Participants |
Secondary
Number of Participants With an Objective Response
Objective responses: Stringent complete response (sCR): CR + normal Free light chain (FLC) ratio and no clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow. Very good partial response (VGPR): serum and urine M protein detectable by immunofixation but not on electrophoresis or \>90% reduction in serum M protein plus urine M protein level \<100 mg/24h. PR: \>50% reduction of serum and 24 h urinary M protein by \>90% or to \<200mg/24h. If unmeasurable, a \>50% decrease in difference between involved and uninvolved FLC levels instead of M protein criteria. if FLC assay was not measurable, a \>50% reduction in plasma cells was required instead of M protein, provided baseline bone marrow plasma cell was \>30%. In addition to the listed criteria, a \>50% reduction in the size of soft tissue plasmacytomas was also required, if present at baseline.
Time frame: On-treatment: From start of treatment till end of trial (EOT) visit, up to 61 weeks. Extended follow-up: From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks.
Population: Treated set (TS): all patients who were administered trial medication.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | No response (stable disease or disease progression) | 5 Participants |
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With an Objective Response | On treatment | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With an Objective Response | On treatment | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With an Objective Response | On treatment | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With an Objective Response | On treatment | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Number of Participants With an Objective Response | On treatment | No response (stable disease or disease progression) | 5 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With an Objective Response | On treatment | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With an Objective Response | On treatment | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With an Objective Response | On treatment | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With an Objective Response | On treatment | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With an Objective Response | On treatment | No response (stable disease or disease progression) | 3 Participants |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | No response (stable disease or disease progression) | 3 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With an Objective Response | On treatment | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With an Objective Response | On treatment | Complete response (CR) | 1 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With an Objective Response | On treatment | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With an Objective Response | On treatment | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Complete response (CR) | 1 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With an Objective Response | On treatment | No response (stable disease or disease progression) | 2 Participants |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | No response (stable disease or disease progression) | 2 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With an Objective Response | On treatment | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With an Objective Response | On treatment | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With an Objective Response | On treatment | No response (stable disease or disease progression) | 3 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With an Objective Response | On treatment | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | No response (stable disease or disease progression) | 3 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (13 μg/d) | Number of Participants With an Objective Response | On treatment | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With an Objective Response | On treatment | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With an Objective Response | On treatment | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With an Objective Response | On treatment | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With an Objective Response | On treatment | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With an Objective Response | On treatment | No response (stable disease or disease progression) | 3 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (25 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | No response (stable disease or disease progression) | 3 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With an Objective Response | On treatment | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With an Objective Response | On treatment | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With an Objective Response | On treatment | No response (stable disease or disease progression) | 4 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With an Objective Response | On treatment | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With an Objective Response | On treatment | Partial response (PR) | 1 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | No response (stable disease or disease progression) | 4 Participants |
| Intravenous Infusion of BI 836909 (50 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Partial response (PR) | 1 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Complete response (CR) | 1 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With an Objective Response | On treatment | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With an Objective Response | On treatment | Complete response (CR) | 1 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With an Objective Response | On treatment | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With an Objective Response | On treatment | No response (stable disease or disease progression) | 3 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | No response (stable disease or disease progression) | 3 Participants |
| Intravenous Infusion of BI 836909 (100 μg/d) | Number of Participants With an Objective Response | On treatment | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With an Objective Response | On treatment | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Stringent complete response (sCR) | 1 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With an Objective Response | On treatment | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | No response (stable disease or disease progression) | 2 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Very good partial response (VGPR) | 0 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With an Objective Response | On treatment | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With an Objective Response | On treatment | Stringent complete response (sCR) | 1 Participants |
| Intravenous Infusion of BI 836909 (200 μg/d) | Number of Participants With an Objective Response | On treatment | No response (stable disease or disease progression) | 2 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With an Objective Response | On treatment | Stringent complete response (sCR) | 5 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With an Objective Response | On treatment | No response (stable disease or disease progression) | 3 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With an Objective Response | On treatment | Very good partial response (VGPR) | 1 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | No response (stable disease or disease progression) | 3 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Partial response (PR) | 1 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Stringent complete response (sCR) | 5 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With an Objective Response | On treatment | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With an Objective Response | On treatment | Partial response (PR) | 1 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Very good partial response (VGPR) | 1 Participants |
| Intravenous Infusion of BI 836909 (400 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Very good partial response (VGPR) | 1 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With an Objective Response | On treatment | Complete response (CR) | 0 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Complete response (CR) | 1 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With an Objective Response | On treatment | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With an Objective Response | On treatment | Partial response (PR) | 1 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Partial response (PR) | 0 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With an Objective Response | On treatment | Very good partial response (VGPR) | 1 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | Stringent complete response (sCR) | 0 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With an Objective Response | On treatment + extended follow-up visits (follow-up | No response (stable disease or disease progression) | 1 Participants |
| Intravenous Infusion of BI 836909 (800 μg/d) | Number of Participants With an Objective Response | On treatment | No response (stable disease or disease progression) | 1 Participants |
Secondary
Progression-free Survival (PFS) - Including Extended Follow up Visits
PFS was defined as time from first treatment with BI 836909 till disease progression or death. Progression was defined according to International Myeloma Working Group (IMWG 2006) response criteria as an increase \>25% from lowest response value in any of the following parameters: -Serum M protein (absolute increase had to be \>0.5 gram/ deciliters (dL)) -Urine M protein (absolute increase had to be \>200 milligram (mg)/24 hour) -Only in patients without measurable serum and urine M protein levels The difference between involved and uninvolved FLC levels. Absolute increase had to be \>10 mg/dL -Bone marrow plasma cell percentage; absolute percentage had to be \>10% -Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas -Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 Millimole/Liter) that was attributed solely to the plasma cell proliferative disorder
Time frame: From start of treatment till the last extended follow-up visit which was scheduled at 12 months after end of treatment, up to 113 weeks.
Population: Treated set (TS): all patients who were administered trial medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Progression-free Survival (PFS) - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Progression-free Survival (PFS) - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Progression-free Survival (PFS) - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (13 μg/d) | Progression-free Survival (PFS) - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (25 μg/d) | Progression-free Survival (PFS) - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (50 μg/d) | Progression-free Survival (PFS) - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (100 μg/d) | Progression-free Survival (PFS) - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (200 μg/d) | Progression-free Survival (PFS) - Including Extended Follow up Visits | NA Months |
| Intravenous Infusion of BI 836909 (400 μg/d) | Progression-free Survival (PFS) - Including Extended Follow up Visits | 7.74 Months |
| Intravenous Infusion of BI 836909 (800 μg/d) | Progression-free Survival (PFS) - Including Extended Follow up Visits | NA Months |
Secondary
Progression-free Survival (PFS) - on Treatment
PFS was defined as time from first treatment with BI 836909 till disease progression or death. Progression was defined according to International Myeloma Working Group (IMWG 2006) response criteria as an increase \>25% from lowest response value in any of the following parameters: -Serum M protein (absolute increase had to be \>0.5 gram/ deciliters (dL)) -Urine M protein (absolute increase had to be \>200 milligram (mg)/24 hour) -Only in patients without measurable serum and urine M protein levels The difference between involved and uninvolved FLC levels. Absolute increase had to be \>10 mg/dL -Bone marrow plasma cell percentage; absolute percentage had to be \>10% -Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas -Development of hypercalcaemia (corrected serum calcium \>11.5 mg/dL or 2.65 Millimole/Liter) that was attributed solely to the plasma cell proliferative disorder.
Time frame: From start of treatment till end of trial (EOT) visit, up to 61 weeks.
Population: Treated set (TS): all patients who were administered trial medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Progression-free Survival (PFS) - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Progression-free Survival (PFS) - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Progression-free Survival (PFS) - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (13 μg/d) | Progression-free Survival (PFS) - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (25 μg/d) | Progression-free Survival (PFS) - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (50 μg/d) | Progression-free Survival (PFS) - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (100 μg/d) | Progression-free Survival (PFS) - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (200 μg/d) | Progression-free Survival (PFS) - on Treatment | NA Months |
| Intravenous Infusion of BI 836909 (400 μg/d) | Progression-free Survival (PFS) - on Treatment | 5.55 Months |
| Intravenous Infusion of BI 836909 (800 μg/d) | Progression-free Survival (PFS) - on Treatment | NA Months |
Secondary
Serum Concentration at Steady State of BI 836909 (Css)
Serum concentration at steady state of BI 836909 (Css).
Time frame: Pharmacokinetic samples were collected at 48:00 hours (h):minutes (min), 168:00, 336:00, 504:00 and 671:50 h after the start of infusion of BI 836909 of the first cycle.
Population: PK Analysis Set (PKS): all evaluable patients in the treated set which provide at least one evaluable observation for at least one PK endpoint.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Infusion of BI 836909 (Total Dose Escalation) | Serum Concentration at Steady State of BI 836909 (Css) | NA picogram/milliliter (pg/mL) | — |
| Intravenous Infusion of BI 836909 (3.2 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 86.5 picogram/milliliter (pg/mL) | — |
| Intravenous Infusion of BI 836909 (6.5 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 90.8 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 41.1 |
| Intravenous Infusion of BI 836909 (13 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 184 picogram/milliliter (pg/mL) | — |
| Intravenous Infusion of BI 836909 (25 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 526 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 34.7 |
| Intravenous Infusion of BI 836909 (50 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 1070 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 67.3 |
| Intravenous Infusion of BI 836909 (100 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 2180 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 34.6 |
| Intravenous Infusion of BI 836909 (200 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 4130 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 30.7 |
| Intravenous Infusion of BI 836909 (400 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 10700 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 55.4 |
| Intravenous Infusion of BI 836909 (800 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 9810 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 47.6 |
| Intravenous Infusion of BI 836909 (200 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 14100 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 121 |
| Intravenous Infusion of BI 836909 (400 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 29900 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 54.3 |
| Intravenous Infusion of BI 836909 (800 μg/d) | Serum Concentration at Steady State of BI 836909 (Css) | 33000 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 41 |