BI 6727 Administered Intravenously Every 3 Weeks in Patie... | NCT02273388

ID	Type	Description	Link
2005-002500-42	EudraCT Number	EudraCT
1230-0001	Other Identifier	BI

BI 6727 Administered Intravenously Every 3 Weeks in Patie... | NCT02273388 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
12 mg BI 6727	Experimental	Drug: BI 6727
24 mg BI 6727	Experimental	Drug: BI 6727
48 mg BI 6727	Experimental	Drug: BI 6727
75 mg BI 6727	Experimental	Drug: BI 6727
125 mg BI 6727	Experimental	Drug: BI 6727
200 mg BI 6727	Experimental	Drug: BI 6727
300 mg BI 6727	Experimental	Drug: BI 6727
300 mg BI 6727 1h2h	Experimental

Name	Type	Description	Arm Group Labels	Other Names
BI 6727	Drug	BI 6727	12 mg BI 6727 125 mg BI 6727 200 mg BI 6727 24 mg BI 6727 300 mg BI 6727 300 mg BI 6727 1h2h

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Tolerated Dose (MTD)	MTD is defined as: the dose of BI 6727 which is one dose tier below that dose at which two or more out of a maximum of six patients experienced dose-limiting toxicity (DLT). At the maximum tolerated dose, no more than one patient out of six patients may experience DLT, i.e. MTD is defined as the highest dose studied for which the incidence of dose-limiting toxicity is no more than 17% (i.e. 1/6 patients) during the first course. DLT is defined as drug related common terminology criteria for adverse events (CTCAE) grade 3 or 4 non haematological toxicity (except emesis or diarrhoea responding to supportive treatment), or drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection, or CTCAE Grade 4 thrombocytopenia .	21 days (first treatment course).

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events (AEs)	Number of participants with adverse events. The events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v.3.0. Grade refers to the severity of adverse event. Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE.	From first drug administration until last drug administration plus 21 days, up to 835 days.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Patients with confirmed diagnosis of advanced, non resectable and / or metastatic solid tumours, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment
Age 18 years or older
Written informed consent consistent with ICH-GCP and local legislation
Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score ¿ 2
Recovery from CTCAE Grade 2 - 4 therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies (except alopecia)

The 18 additional patients recruited at the MTD must also meet the following criterion:
Measurable tumour deposits (RECIST) by one or more techniques (CT, MRI)

Exclusion criteria:

Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
Pregnancy or breastfeeding
Active infectious disease or known chronic Hepatitis B/Hepatitis C infection
Clinical evidence of active brain or leptomeningeal disease during the past 12 months
Second malignancy currently requiring active therapy
Absolute neutrophil count less than 1500 / mm3
Platelet count less than 100 000 / mm3
Bilirubin greater than 1.5 mg / dl (> 26 ¿mol / L, SI unit equivalent)
Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
Serum creatinine greater than 1.5 mg / dl (> 132 ¿mol / L, SI unit equivalent)
Known history of relevant QT-prolongation, e.g. long QT-syndrome
Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug)
Chemo-, radio or immunotherapy within the past four weeks before start of therapy or concomitantly with this trial. This restriction does not apply to steroids and bisphosphonates.
Patients unable to comply with the protocol
Active alcohol or drug abuse

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1230.1.32002 Boehringer Ingelheim Investigational Site		Brussels			Belgium
1230.1.32001 Boehringer Ingelheim Investigational Site

Arm/Group Information

ID	Title	Description
FG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
FG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
FG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
FG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
FG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
FG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
FG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
FG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
FG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
FG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
FG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
FG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED	Started are treated	FG0004 subjects FG0013 subjects FG0023 subjects FG0032 subjects FG004
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
NOT COMPLETED		FG0004 subjects FG0013 subjects FG0023 subjects FG0032 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
BG001	24 mg BI 6727

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Tolerated Dose (MTD)

MTD is defined as: the dose of BI 6727 which is one dose tier below that dose at which two or more out of a maximum of six patients experienced dose-limiting toxicity (DLT). At the maximum tolerated dose, no more than one patient out of six patients may experience DLT, i.e. MTD is defined as the highest dose studied for which the incidence of dose-limiting toxicity is no more than 17% (i.e. 1/6 patients) during the first course.

DLT is defined as drug related common terminology criteria for adverse events (CTCAE) grade 3 or 4 non haematological toxicity (except emesis or diarrhoea responding to supportive treatment), or drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection, or CTCAE Grade 4 thrombocytopenia .

Treated Set (TS): All patients who received at least one dose of BI 6727.

Posted

Number

Milligram (mg)

21 days (first treatment course).

ID	Title	Description
OG000	BI 6727

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Boehringer Ingelheim, Call Center	Boehringer Ingelheim	1-800-243-0127		clintriage.rdg@boehringer-ingelheim.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 3, 2005	Apr 6, 2022	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Aug 7, 2009	Apr 6, 2022	SAP_001.pdf

ID	Term
D009369	Neoplasms

ID	Term
C541363	BI 6727

Title

Denominators

Categories

Title	Measurements
	BG00034.5(19 to 47) BG00153.0(43 to 62) BG00243.0(37 to 68) BG00357.0(51 to 63) BG00458.5(48 to 73) BG00565.0(59 to 71) BG00655.0(24 to 79) BG00754.5(41 to 66) BG00860.5(44 to 78) BG00961.0(57 to 79) BG01060.0(39 to 79) BG01150.0(41 to 59) BG01258.0(19 to 79)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0003 BG0013 BG0020 BG0032 BG0041 BG0051 BG0066 BG0071 BG0082 BG0093 BG0105 BG0110 BG01227
Male	BG0001 BG0010 BG0023 BG0030 BG004

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG0020 BG0030 BG0040 BG0050 BG0060 BG0070 BG0080 BG0090 BG0100 BG0110 BG0120
Asian	BG0000 BG0010 BG0020 BG0030 BG004
Native Hawaiian or Other Pacific Islander	BG0000 BG0010 BG0020 BG0030 BG004
Black or African American	BG0000 BG0010 BG0020 BG0030 BG004
White	BG0004 BG0013 BG0023 BG0032 BG004
More than one race	BG0000 BG0010 BG0020 BG0030 BG004
Unknown or Not Reported	BG0000 BG0010 BG0020 BG0030 BG004

Secondary

Number of Participants With Adverse Events (AEs)

Number of participants with adverse events. The events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v.3.0.

Grade refers to the severity of adverse event. Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE.

Treated Set (TS): All patients who received at least one dose of BI 6727.

Posted

Count of Participants

Participants

From first drug administration until last drug administration plus 21 days, up to 835 days.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Grade 1

Title	Measurements
	OG0001 OG0011 OG0021 OG003

Secondary

Number of Participants With Clinically Relevant Abnormalities

Number of participants with clinically relevant abnormalities, occurring in >5% of the total number of participants, is reported.

Clinically relevant post baseline values with Common Terminology Criteria for Adverse Events (CTCAE) grades:

CTCAE grade ≥4 for White blood cell count (WBC) , Neutrophils (NEUT), NEUABS Lymphocytes (LMPH) if baseline CTCAE grade is not 4
CTCAE grade ≥3 for Haemoglobin (HGB), Platelets count (PLTCT), Alkaline phosphatase (ALKP), serum glutamic-oxaloacetic-transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total bilirubin (TBILI), if baseline CTCAE grade is ≥3 increases of one grade
CTCAE grade ≥2 for other parameters, if baseline CTCAE grade is ≥2 increases of at least one grade

Treated Set (TS): All patients who received at least one dose of BI 6727.

Posted

Count of Participants

Participants

From baseline to the last value on treatment, up to 814 days.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Haematocrit

Title	Measurements
	OG0001 OG0012 OG0021 OG003

Secondary

Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score

ECOG score: The scale of ECOG score is defined as a six point categorical scale as described ranging from 0 (asymptomatic) to 5 (death). ECOG score change from baseline to end of treatment is calculated, and defined as

= ECOG score at end of treatment - ECOG score at baseline.

Scale of ECOG score change:

The ECOG score changes from baseline score are categorized on a three point categorical scale: Improved, unchanged, and deteriorated. Improvement or deterioration of performance status required a decrease or an increase from baseline, respectively, of at least one point on the ECOG scale. The number of patients per category ("improved", "unchanged", "deteriorated" "unknown") is reported.

Treated Set (TS): All patients who received at least one dose of BI 6727.

Posted

Count of Participants

Participants

At baseline and at end of treatment (up to 814 days).

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Improved

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Secondary

Electrocardiogram (ECG) - QTcF Change From Baseline

Electrocardiogram (ECG) - QTcF change from baseline. QTcF intervals form the ECGs were analysed for changes during and after intravenous infusion of BI 300 mg dose over 1 hours and over 2 hours. For baseline ECG, the combined baseline, defined as the mean of the 2 triplicates at the time-point closest to but prior to the start of the infusion of both treatment courses, i.e. a common baseline is used for both treatment courses, was used. Mean is adjusted mean.

Abbreviations:

QTcF: QT interval, corrected for heart rate according to Fridericia's formula (seconds) = measured QT / (cube root of preceding RR interval) QT: Interval from the beginning of the Q wave to the end of the T wave on an ECG (seconds).

CfB: Change from baseline.

QT extension cohort: Patients treated with 300 mg BI6727 to investigate QTc changes, according to two different treatment schedules in course 1 and course 2, (300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h). Results are reported for 300 mg over 1 hour infusion vs. 300 mg over 2 hours infusion. Only participants with non-missing data were included in the analysis.

Posted

Mean

90% Confidence Interval

Millisecond (ms)

At baseline and 5 minutes before infusion end, 1 hour after end of infusion and at 4 and 12 hours after start of infusion, at course 1.

ID	Title	Description
OG000	300 mg BI 6727 1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h). QT extension cohort.
OG001	300 mg BI 6727 2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hours (2h). QT extension cohort.

Units	Counts
Participants	OG00013 OG00111

Title

Denominators

Categories

CfB to 5 minutes before infusion end

Title	Measurements
	OG00017.79(13.68 to 21.90) OG00113.23(8.83 to 17.64)

CfB to 1 hours after infusion end

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Change from baseline to 5 minutes before infusion end. Linear mixed model with sequence, course, treatment (both infusion types i.e. 1 hour duration and 2 hour duration) and time as fixed effects and treatment*time as interaction effect, as well as the continuous , fixed covariate of baseline value.					Difference of adjusted means	-4.56	Standard Error of the Mean	3.61	2-Sided	90	-10.59	1.48			Comparison vs. 1 hour infusion [2h-1h]		Other

Secondary

Vital Signs - Blood Pressure

Systolic blood pressure and diastolic blood pressure are reported.

Treated Set (TS): All patients who received at least one dose of BI 6727.

Posted

Median

Full Range

Millimeter of mercury (mmHg)

At baseline.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Systolic blood pressure

Title	Measurements
	OG000126(110 to 155) OG001124(107 to 148) OG002124(110 to 134) OG003

Secondary

Vital Signs - Pulse Rate

Pulse rate is reported.

Treated Set (TS): All patients who received at least one dose of BI 6727.

Posted

Median

Full Range

Beats per minute (bpm)

At baseline.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG00088(76 to 92) OG00180(72 to 98) OG00288(73 to 92) OG003

Secondary

Number of Participants With Unconfirmed Best Overall Response

For solid tumours, evaluation of tumour response was assessed according to the Response Evaluation Criteria in Solid Tumours (RECIST) definition. The overall response of target and non-target lesions together with or without the appearance of new lesions as reported by the investigator was assessed on a four point categorical scale as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to the RECIST criteria. In order to best handle measurements that were non-evaluable (NEV) a modified version of the RECIST criteria was used. If a RECIST overall response was deemed NEV, it could be further classified into non-evaluable clinically progressive disease (NEVCPD ) or non-evaluable clinically non-progressive disease (NEVCNPD), depending on the subjective assessment of the investigator.

Treated Set (TS): All patients who received at least one dose of BI 6727.

Posted

Count of Participants

Participants

Up to 814 days.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Complete response

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Secondary

Number of Participants With Progression

Number of participants with progression of disease.

Progressive disease is defined according to the Response Evaluation Criteria in Solid Tumours (RECIST) as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter.

Treated Set (TS): All patients who received at least one dose of BI 6727.

Posted

Count of Participants

Participants

Up to 814 days.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0003 OG0013 OG0023 OG003

Secondary

Maximum Concentration of BI 6727 in Plasma (Cmax)

Maximum concentration of BI 6727 in plasma (Cmax).

Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h:

For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1*, 2, 4, 8, 24 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1*, 2, 3, 4 and 24 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

Treated Set (TS): All patients who received at least one dose of BI 6727. Only patients with non-missing values were included in the analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram/ Milliliter (ng/mL)

At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG00018.8± 14.3 OG00150.7± 12.4 OG00291.1± 17.6 OG003

Secondary

Time From Dosing to Maximum Concentration (Tmax)

Time from dosing to maximum concentration (tmax).

Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h:

For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1*, 2, 4, 8, 24 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1*, 2, 3, 4 and 24 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

Treated Set (TS): All patients who received at least one dose of BI 6727. Only patients with non-missing values were included in the analysis.

Posted

Median

Inter-Quartile Range

Hours (h)

At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.667(0.500 to 0.750) OG0010.750(0.750 to 1.25) OG0020.500(0.250 to 0.533) OG003

Secondary

Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)

Area under the concentration-time curve of BI 6727 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf).

Only patients in the treated set who had non-missing values were included in the analysis. For arms with 0 patients analysed: No sufficient data had been collected to determine the terminal half-life T1/2, which is needed to analyse the PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram * Hours / Milliliter (ng*h/mL)

0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 and 504 hours after start of infusion. (*Immediately prior to end of infusion of BI 6727).

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG000149± 31.6 OG001380± 38.9 OG002778± 25.1 OG003

Secondary

Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz)

Area under the concentration-time curve of BI 6727 in plasma over the time interval from 0 to the last quantifiable time point tz (AUC0-tz).

Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h:

For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1*, 2, 4, 8, 24 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1*, 2, 3, 4 and 24 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

Treated Set (TS): All patients who received at least one dose of BI 6727. Only patients with non-missing values were included in the analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram * Hours / Milliliter (ng*h/mL)

0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 and 504 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG000101± 39.0 OG001320± 52.0 OG002636± 25.8 OG003

Secondary

Terminal Rate Constant in Plasma (λz)

Terminal rate constant in plasma (λz).

Posted

Geometric Mean

Geometric Coefficient of Variation

1 / hour

At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.00715± 32.0 OG0010.00649± 16.9 OG0020.00446± 40.1 OG003

Secondary

Terminal Half-life of the Analyte in Plasma (t1/2)

Terminal half-life of the analyte in plasma (t1/2).

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours (h)

At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG00096.9± 32.0 OG001107± 16.9 OG002156± 40.1 OG003

Secondary

Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT)

Mean residence time of BI 6727 in the body after intravenous administration (MRT).

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours (h)

At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG000113± 33.6 OG001127± 11.3 OG002174± 36.2 OG003

Secondary

Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL)

Total clearance of BI 6727 in the plasma after intravascular adminstration (CL).

Posted

Geometric Mean

Geometric Coefficient of Variation

Milliliter/Minute (mL/min)

At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001140± 32.2 OG001876± 44.4 OG002924± 20.2 OG003

Secondary

Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss)

Apparent volume of distribution at steady state following intravascular administration (Vss).

Posted

Geometric Mean

Geometric Coefficient of Variation

Liter

At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0007730± 30.8 OG0016670± 46.0 OG0029630± 36.7 OG003

Secondary

Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz)

Apparent volume of distribution during the terminal phase λz following an intravascular dose (Vz).

Posted

Geometric Mean

Geometric Coefficient of Variation

Liter (L)

At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0009530± 34.8 OG0018100± 52.6 OG00212400± 46.2 OG003

Secondary

Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24)

Amount of BI 6727 that is eliminated in urine from the time point 0 to time point 24 hours (Ae0-24).

Only patients in the treated set (TS) who had non-missing values were included in the analysis. Descriptive statistics for the 200 mg group could not be evaluated, since plasma concentrations of BI 6727 was only quantifiable in less than two-thirds of the patients. Descriptive statistics is calculated in case that 2/3 patients of total could be evaluated, as defined in the trial statistical analysis plan (TSAP).

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram (µg)

5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0012 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG000299± 12.4 OG001493± 104 OG0021580± 12.9 OG003

Secondary

Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48)

Amount of BI 6727 that is eliminated in urine from the time point 0 to time point 48 hours (Ae0-48).

Only patients in the treated set (TS) who had non-missing values were included in the analysis. Descriptive statistics for 200mg and 350mg group could not be evaluated, since plasma concentrations of BI 6727 was only quantifiable in less than two-thirds of the patients, respectively. Descriptive statistics is calculated in case that 2/3 patients of total could be evaluated, as defined in the trial statistical analysis plan (TSAP).

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram (µg)

5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0012 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG000379± 26.1 OG001618± 105 OG0022030± 15.7 OG003

Secondary

Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24)

Fraction of BI 6727 (percentage of dose) eliminated in urine from time point 0 to time point 24 hours (Fe0-24).

Only patients in the treated set (TS) who had non-missing values were included in the analysis. Descriptive statistics for 200 mg group could not be evaluated, since plasma concentrations of BI 6727 was only quantifiable in less than two-thirds of the patients. Descriptive statistics is calculated in case that 2/3 patients of total could be evaluated, as defined in the trial statistical analysis plan (TSAP).

Posted

Geometric Mean

Geometric Coefficient of Variation

Percentage of dose

5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0003 OG0012 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0003.10± 12.1 OG0012.38± 101 OG0023.65± 12.8 OG003

Secondary

Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48)

Fraction of BI 6727 (percentage of dose) eliminated in urine from time point 0 to time point 48 hours (Fe0-48).

Posted

Geometric Mean

Geometric Coefficient of Variation

Percentage of dose

5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0012 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0003.75± 27.0 OG0012.98± 102 OG0024.71± 16.2 OG003

Secondary

Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24)

Renal clearance of BI 6727 from the time point 0 to time point 24 hours (CLr,0-24).

Posted

Geometric Mean

Geometric Coefficient of Variation

Milliliter/minutes (mL/min)

5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0012 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG000106± 11.5 OG00187.6± 67.8 OG002127± 11.8 OG003

Secondary

Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48)

Renal clearance of BI 6727 from the time point 0 to time point 48 hours (CLr,0-48).

Only patients in the treated set with non-missing values. For arms with 0 patients analysed: No sufficient data had been collected to determine the terminal half-life T1/2, which is needed to analyse the PK data. Descriptive statistics for 200 and 350 mg group could not be evaluated, since plasma concentrations of BI 6727 was only quantifiable in less than 2/3 of patients, respectively. Descriptive statistics is calculated in case that 2/3 patients of total could be evaluated as defined in TSAP.

Posted

Geometric Mean

Geometric Coefficient of Variation

Milliliter/minutes (mL/min)

5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.

ID	Title	Description
OG000	12 mg BI 6727	12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG001	24 mg BI 6727	24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG002	48 mg BI 6727	48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG003	75 mg BI 6727	75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG004	125 mg BI 6727	125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG005	200 mg BI 6727	200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG006	300 mg BI 6727	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG007	300 mg BI 6727 1h2h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG008	300 mg BI 6727 2h1h	300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort.
OG009	350 mg BI 6727	350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG010	400 mg BI 6727	400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).
OG011	450 mg BI 6727	450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients).

Units	Counts
Participants	OG0004 OG0012 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG00099.8± 5.89 OG00180.6± 62.2 OG002118± 13.5 OG003

Diastolic blood pressure

Title	Measurements
	OG00074(60 to 80) OG00180(68 to 90) OG00278(78 to 85) OG00375(70 to 80) OG00471.5(58 to 80) OG00576(72 to 90) OG00680(69 to 98) OG00778.5(67 to 89) OG00886.5(60 to 100) OG00982(70 to 90) OG01081.5(45 to 100) OG01175(70 to 80)