Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
The trial will be performed to evaluate whether BI 2536 may be effective in the treatment of advanced or metastatic NSCLC of stage IIIB or IV in patients who relapsed after or failed first-line therapy. A secondary aim is to identify the most suitable dosage schedule for the further Phase II and III clinical programme of BI 2536. To achieve this objective two dosage schedules are compared.
Interventions
DRUGBI 2536
Intravenous Infusion
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
male or female patients aged 18 years or older with histologically or cytologically confirmed advanced or metastatic NSCLC of stage IIIB or IV, who relapsed or failed prior first-line chemotherapy for advanced or metastatic disease. At least one tumour lesion must be present that can accurately be measured by magnetic resonance imaging (MRI), or computed tomography (CT) in at least one dimension (longest diameter to be recorded) as 20 mm or greater with conventional techniques or as 10 mm or greater with spiral CT scan. Life expectancy of at least three months; Eastern co-operative oncology group (ECOG) performance score of 2 or less and written informed consent which must be consistent with international conference on harmonisation good clinical practice (ICH-GCP) and local legislation
Exclusion criteria
persistence of toxicities of prior anti cancer therapies which are deemed to be clinically relevant, known secondary malignancy requiring therapy, brain metastases which are symptomatic or require therapy, absolute neutrophil count less than 1,500/mm3, platelet count less than 100,000/mm3, haemoglobin less than 9 mg/dl, aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal, or AST or ALT greater than 5 times the upper limit of normal in case of known liver metastases, bilirubin greater than 1.5 mg/dl, serum creatinine greater than 2.0 mg/dl, concomitant intercurrent illnesses that would limit compliance with trial requirement or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, chemo-, hormone- or immunotherapy within the past four weeks or within less than four half-life times of the previous drug prior to treatment with the trial drug (whatever is the longest period), radiotherapy within the past four weeks prior to treatment with the trial drug, men or women who are sexually active and unwilling to use a medically acceptable method of contraception during the trial, pregnancy or lactation, treatment with any other investigational drug within the past four weeks or within less than four half-life times of the investigational drug before treatment with the trial drug (whatever is the longest period), patient unable to comply with the protocol, patients who are considered eligible by the investigator for other second-line chemotherapy, radiotherapy or immunotherapy, patients who have received more than two lines of prior anti-tumour therapy for advanced or metastatic non small cell lung cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Central Review of the Tumour Images | assessed at baseline, then every 6 weeks (every second treatment course) until disease progression or start of any other anti-tumour therapy or death or individual participant's end of trial, up to 533 days | The best overall response was the best response recorded from start of treatment until the participant progressed, received any other anti-tumour therapy, died or until the individual participant's end of trial. Number of participants with 'Objective tumour response evaluated according to RECIST 1.0 by central review of the tumour images = Yes' are reported. Objective response is complete response (disappearance of all target lesions) or partial response (at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter). Changes in tumour measurements were confirmed by repeat assessments that had to be performed 6 weeks after the criteria for response had been first met. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | every 6 weeks (every second treatment course), up to 599 days | Overall survival defined as time from date of randomisation until date of death from any cause. Participants alive at the time of analysis were censored at the date of the last trial visit or last date of follow-up, whatever came last. |
| Duration of Overall Response | assessed at baseline, then every 6 weeks (every second treatment course) until disease progression or start of any other anti-tumour therapy or death or individual participant's end of trial, up to 533 days | For participants who showed an overall tumour response of complete response (CR, disappearance of all target lesions) or partial response (PR, at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter), 'duration of overall response' was defined as the time from the first date where measurement criteria were met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease (PD) was objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started). Tumour response was evaluated based on local radiological images according to RECIST version 1.0 (agreed upon by independent review). The number of participants with an CR or PR who experienced the event 'recurrent or PD' is reported instead of the time-to-event data with unit of time as the number analyzed was too small to perform a Kaplan-Meier analysis. |
| Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Investigator | assessed at baseline, then every 6 weeks (every second treatment course) until disease progression or start of any other anti-tumour therapy or death or individual participant's end of trial, up to 533 days | The best overall response was the best response recorded from start of treatment until the participant progressed, received any other anti-tumour therapy, died or until the individual participant's end of trial. 'Objective tumour response evaluated according to RECIST 1.0 by investigator' is 'Yes' if the best overall response is either complete response (CR, disappearance of all target lesions) or partial response (PR, at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter). Otherwise it is 'No'. To be assigned a status of 'partial response' or 'complete response', changes in tumour measurements were confirmed by repeat assessments that had to be performed six weeks after the criteria for response had been first met. Number of participants with 'Objective tumour response evaluated according to RECIST 1.0 by investigator = Yes' are reported. |
| Time-to-deterioration for Symptom Score 'Cough' Assessed on Question 1 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | baseline and every 3 weeks (prior to the first administration of BI 2536 in a treatment course comprising 3 weeks), up to 539 days | Time to deterioration for cough \[days\] was defined as the time from randomization to deterioration in score for the symptom 'cough'. Participants were considered to have deteriorated if a 10-point increase from the baseline score at any time point after baseline was observed. Participants who died before deteriorating were analyzed as having deteriorated at the time of death. Participants with disease progression without deterioration in score were censored at the time of the last scale measurement. Participants with no QoL assessments were censored at day 1. The score for symptom 'cough' was based on Question 1 on the lung cancer module QLQ LC13 of the EORTC QLQ C30 Version 3.0. A linear transformation was used to standardize the raw scores, so that scores range from 0 to 100. A high score represents a higher (worse) level of the symptom 'cough'. |
| Time-to-deterioration for Symptom Score 'Dyspnoea' Assessed on the Composite of Questions 3-5 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | baseline and every 3 weeks (prior to the first administration of BI 2536 in a treatment course comprising 3 weeks), up to 539 days | Time to deterioration for dyspnoea \[days\] was defined as the time from randomization to deterioration in score for the symptom 'dyspnoea'. Participants were considered to have deteriorated if a 10-point increase from the baseline score at any time point after baseline was observed. Participants who died before deteriorating were analyzed as having deteriorated at the time of death. Participants with disease progression without deterioration in score were censored at the time of the last scale measurement. Participants with no QoL assessments were censored at day 1. The score for symptom 'dyspnoea' was based on the composite of Questions 3-5 on the lung cancer module QLQ LC13 of the EORTC QLQ C30 Version 3.0. A linear transformation was used to standardize the raw scores, so that scores range from 0 to 100. A high score represents a higher (worse) level of the symptom 'dyspnoea'. |
| Time-to-deterioration for Symptom Score 'Pain' Assessed on the Composite of Questions 9 and 19 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | baseline and every 3 weeks (prior to the first administration of BI 2536 in a treatment course comprising 3 weeks), up to 539 days | Time to deterioration for pain \[days\] was defined as the time from randomization to deterioration in score for the symptom 'pain'. Participants were considered to have deteriorated if a 10-point increase from the baseline score at any time point after baseline was observed. Participants who died before deteriorating were analyzed as having deteriorated at the time of death. Participants with disease progression without deterioration in score were censored at the time of the last scale measurement. Participants with no QoL assessments will be censored at day 1. The score for symptom 'pain' was based on the composite of Questions 9 and 19 of the EORTC QLQ C30 Version 3.0. A linear transformation was used to standardize the raw scores, so that scores range from 0 to 100. A high score represents a higher (worse) level of the symptom 'pain'. |
| BI 2536 Plasma Concentrations After Intravenous Infusion of 200 Milligram BI 2536 on Day 1 in Treatment Course 1 | on day 1 in treatment course 1: 0.5 hour (h) , 1 h, 2 h, 4 h, 120 h post-dose (planned times) | BI 2536 plasma concentrations after intravenous infusion of 200 milligram BI 2536 on day 1 in treatment course 1. Geometric Coefficient of Variation reported in percentage \[%\]. |
| Progression Free Survival | every 6 weeks (every second treatment course), up to 419 days | Progression-free survival defined as time from date of randomisation until date of imaging indicating progressive disease (PD) as assessed by the independent central imaging review (according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0) or date of investigator assessment of clinical progression or date of progressive disease recorded during the follow-up period or death date, whatever comes first. Participants without documented progression at the time of analysis were censored at the date of the last visit. Per RECIST version 1.0 for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): PD, At least a 20% increase in the sum of the longest diameter (SoD) of target lesions taking as reference the smallest SoD of target lesions recorded since the treatment started or the appearance of one or more new lesions. |
| Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | On-treatment period, that is, from first administration of the trial drug until 3 weeks after the last administration of the trial drug, up to 428 days | Number of participants with adverse events categorized by common terminology criteria for adverse events (CTCAE) grades (version 3.0) are reported. |
| Incidence of Dose Limiting Toxicity (DLT) | On-treatment period, that is, from first administration of the trial drug until 3 weeks after the last administration of the trial drug, up to 428 days | Dose limiting toxicity was defined as drug related common terminology criteria for adverse events (CTCAE) grade 3 or greater non haematological toxicity (excluding untreated nausea, vomiting or diarrhoea) or drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection or CTCAE grade 4 thrombocytopenia. Number of participants with DLT is reported. |
| Number of Participants With Neutropenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 | On-treatment period, that is, from first administration of the trial drug until 3 weeks after the last administration of the trial drug, up to 428 days | Number of participants with neutropenia of common terminology criteria for adverse events (CTCAE) grade 3 or 4. |
| Number of Participants With Thrombocytopenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 | On-treatment period, that is, from first administration of the trial drug until 3 weeks after the last administration of the trial drug, up to 428 days | Number of participants with thrombocytopenia of common terminology criteria for adverse events (CTCAE) grade 3 or 4. |
| Change From Baseline in Systolic/Diastolic Blood Pressure at Individual Participant's End-of-trial Visit | baseline, date of individual participant's end of trial visit which was 533 days after start of treatment at the latest | Change from baseline in systolic/diastolic blood pressure at individual participant's end-of-trial visit. |
| Change From Baseline in Pulse Rate at Individual Participant's End-of-trial Visit | baseline, date of individual participant's end of trial visit which was 533 days after start of treatment at the latest | Change from baseline in pulse rate at individual participant's end-of-trial visit. |
| BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | on day 1 in treatment course 1: 1 hour (h), 2 h, 23.92 h, 25 h, 47.92 h, 48.5 h, 49 h, 50 h, 52 h, 120 h post-dose (planned times) | BI 2536 plasma concentrations after intravenous infusion of 50 / 60 milligram BI 2536 on day 1 in treatment course 1. Geometric Coefficient of Variation reported in percentage \[%\]. |
Countries
Germany
Participant flow
Recruitment details
An open-label, randomized, parallel-group, phase II clinical trial to investigate the efficacy, safety and pharmacokinetics of a single dose of 200 milligram (mg) BI 2536 administered intravenously in comparison to 50 / 60 mg BI 2536 administered intravenously on days 1, 2 and 3 in patients with advanced or metastatic non small cell lung cancer.
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. Abbreviation: Common Terminology Criteria for Adverse Events version 3.0 (CTCAE)
Participants by arm
| Arm | Count |
|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) A single dose of 200 mg BI 2536 on day one of each treatment course (comprising 21 days including the day of administration) was administered as an intravenous infusion over a period of 60 minutes. Each participant was planned to receive at least 2 treatment courses, in case of clinical benefit (i.e., at least stable disease and acceptable tolerability) the participants could continue therapy. Trial drug administration was stopped temporarily in case of dose limiting toxicity (DLT). Participants could continue therapy only if recovery from DLT occurred and only with a dose reduced by up to 50 mg. Dose reduction was allowed only once for a participant during the whole trial. If a participant had experienced a second episode of DLT with the reduced dose or had not recovered from DLT then the participant was withdrawn from the trial. A participant who continued therapy with BI 2536 beyond course 2 could be treated with a higher dose in case of non-progression and good tolerability. | 48 |
| 50 Milligram BI 2536 (Day 1 - Day 3) A single dose of 50 mg BI 2536 on days 1, 2 and 3 of each treatment course (comprising 21 days including the days of administration) was administered as an intravenous infusion over a period of 60 minutes. Each participant was planned to receive at least 2 treatment courses, in case of clinical benefit (i.e., at least stable disease and acceptable tolerability) the participants could continue therapy with the trial drug. Trial drug administration was stopped temporarily in case of dose limiting toxicity (DLT). Participants could continue therapy only if recovery from DLT (to CTCAE levels which allowed further therapy) occurred and only with a dose reduced by up to 10 mg. Dose reduction was allowed only once for a participant during the whole trial. If a participant had experienced a second episode of DLT with the reduced dose or the participant had not recovered from DLT then the participant was withdrawn from the trial. A participant who continued therapy with BI 2536 beyond course 2 could be treated with a higher dose in case of non-progression and good tolerability. | 26 |
| 60 Milligram BI 2536 (Day 1 - Day 3) After implementation of protocol amendment 2 a single dose of 60 mg BI 2536 on days 1, 2 and 3 of each treatment course (comprising 21 days including the days of administration) was administered as an intravenous infusion over a period of 60 minutes. Each participant was planned to receive at least 2 treatment courses, in case of clinical benefit (i.e., at least stable disease and acceptable tolerability) the participants could continue therapy with the trial drug. Trial drug administration was stopped temporarily in case of dose limiting toxicity (DLT). Participants could continue therapy only if recovery from DLT (to CTCAE levels which allowed further therapy) occurred and only with a dose reduced by up to 10 mg. Dose reduction was allowed only once for a participant during the whole trial. If a participant had experienced a second episode of DLT with the reduced dose or the participant had not recovered from DLT then the participant was withdrawn from the trial. A participant who continued therapy with BI 2536 beyond course 2 could be treated with a higher dose in case of non-progression and good tolerability. | 21 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event other than Dose Limiting Toxicity | 6 | 1 | 2 |
| Overall Study | Bone metastasis | 1 | 0 | 0 |
| Overall Study | Increase of tumour markers | 0 | 1 | 0 |
| Overall Study | Investigator's and participant's decision to stop treatment with BI 2536 | 1 | 0 | 0 |
| Overall Study | Investigator's and participant's decision to stop treatment with BI 2536 after 6 cycles | 1 | 0 | 0 |
| Overall Study | Investigator's decision to stop treatment with BI 2536 | 0 | 1 | 0 |
| Overall Study | Investigator's decision to stop treatment with BI 2536 after 6 cycles | 2 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Not treated with BI 2536 | 1 | 0 | 0 |
| Overall Study | Participant's decision to stop treatment with BI 2536 | 2 | 0 | 1 |
| Overall Study | Participant's decision to stop treatment with BI 2536 after 6 cycles | 0 | 0 | 1 |
| Overall Study | Progressive disease | 35 | 22 | 17 |
Baseline characteristics
| Characteristic | 200 Milligram (mg) BI 2536 (Day 1) | 50 Milligram BI 2536 (Day 1 - Day 3) | 60 Milligram BI 2536 (Day 1 - Day 3) | Total |
|---|---|---|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 9.1 | 61.2 years STANDARD_DEVIATION 9.1 | 62.5 years STANDARD_DEVIATION 12 | 61.8 years STANDARD_DEVIATION 9.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 48 Participants | 25 Participants | 21 Participants | 94 Participants |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 4 Participants | 28 Participants |
| Sex: Female, Male Male | 33 Participants | 17 Participants | 17 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 35 / 48 | 20 / 26 | 16 / 21 | 36 / 47 |
| other Total, other adverse events | 44 / 48 | 24 / 26 | 19 / 21 | 43 / 47 |
| serious Total, serious adverse events | 20 / 48 | 8 / 26 | 12 / 21 | 20 / 47 |
Outcome results
Primary
Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Central Review of the Tumour Images
The best overall response was the best response recorded from start of treatment until the participant progressed, received any other anti-tumour therapy, died or until the individual participant's end of trial. Number of participants with 'Objective tumour response evaluated according to RECIST 1.0 by central review of the tumour images = Yes' are reported. Objective response is complete response (disappearance of all target lesions) or partial response (at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter). Changes in tumour measurements were confirmed by repeat assessments that had to be performed 6 weeks after the criteria for response had been first met.
Time frame: assessed at baseline, then every 6 weeks (every second treatment course) until disease progression or start of any other anti-tumour therapy or death or individual participant's end of trial, up to 533 days
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Central Review of the Tumour Images | 2 Number of Participants |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Central Review of the Tumour Images | 0 Number of Participants |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Central Review of the Tumour Images | 0 Number of Participants |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Central Review of the Tumour Images | 0 Number of Participants |
Comparison: Efficacy of BI 2536 was evaluated by comparing the tumour response rate of the present trial with the tumour response rate published for patients with the same stage of disease treated with placebo. For this, treatment groups 'BI 2536 200 mg' and 'combination of treatment group 50 mg BI 2536 (day 1 - day 3) and 60 mg BI 2536 (day 1 - day 3)' were pooled together and compared to historical placebo.p-value: 0.0548One-sided exact binomial test
Secondary
BI 2536 Plasma Concentrations After Intravenous Infusion of 200 Milligram BI 2536 on Day 1 in Treatment Course 1
BI 2536 plasma concentrations after intravenous infusion of 200 milligram BI 2536 on day 1 in treatment course 1. Geometric Coefficient of Variation reported in percentage \[%\].
Time frame: on day 1 in treatment course 1: 0.5 hour (h) , 1 h, 2 h, 4 h, 120 h post-dose (planned times)
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants that were not randomized.~Plasma concentrations below the limit of quantification were not used.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 200 Milligram BI 2536 on Day 1 in Treatment Course 1 | 0.5 hour post-dose (planned time) | 614 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 40.2 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 200 Milligram BI 2536 on Day 1 in Treatment Course 1 | 1 hour post-dose (planned time) | 589 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 52.8 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 200 Milligram BI 2536 on Day 1 in Treatment Course 1 | 2 hour post-dose (planned time) | 160 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 37.1 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 200 Milligram BI 2536 on Day 1 in Treatment Course 1 | 4 hour post-dose (planned time) | 110 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 37.1 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 200 Milligram BI 2536 on Day 1 in Treatment Course 1 | 120 hour post-dose (planned time) | 3.07 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 65.5 |
Secondary
BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1
BI 2536 plasma concentrations after intravenous infusion of 50 / 60 milligram BI 2536 on day 1 in treatment course 1. Geometric Coefficient of Variation reported in percentage \[%\].
Time frame: on day 1 in treatment course 1: 1 hour (h), 2 h, 23.92 h, 25 h, 47.92 h, 48.5 h, 49 h, 50 h, 52 h, 120 h post-dose (planned times)
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.~Plasma concentrations below the limit of quantification were not used.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 1 hour post-dose (planned time) | 114 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 38.7 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 2 hour post-dose (planned time) | 35.9 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 54.6 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 23.92 hour post-dose (planned time) | 4.89 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 36.6 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 25 hour post-dose (planned time) | 122 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 49.4 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 47.92 hour post-dose (planned time) | 7.21 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 37.6 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 48.5 hour post-dose (planned time) | 134 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 32.4 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 49 hour post-dose (planned time) | 121 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 61.1 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 50 hour post-dose (planned time) | 41.4 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 34.6 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 52 hour post-dose (planned time) | 29.2 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 30.7 |
| 200 Milligram (mg) BI 2536 (Day 1) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 120 hour post-dose (planned time) | 2.42 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 53.6 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 50 hour post-dose (planned time) | 51.2 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 59.3 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 1 hour post-dose (planned time) | 139 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 70.6 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 48.5 hour post-dose (planned time) | 170 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 33.5 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 2 hour post-dose (planned time) | 39.8 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 56.7 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 120 hour post-dose (planned time) | 3.19 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 57.7 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 23.92 hour post-dose (planned time) | 5.88 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 49.5 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 49 hour post-dose (planned time) | 172 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 63.8 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 25 hour post-dose (planned time) | 152 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 76.3 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 52 hour post-dose (planned time) | 41.2 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 92 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1 | 47.92 hour post-dose (planned time) | 10.2 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 82.4 |
Secondary
Change From Baseline in Pulse Rate at Individual Participant's End-of-trial Visit
Change from baseline in pulse rate at individual participant's end-of-trial visit.
Time frame: baseline, date of individual participant's end of trial visit which was 533 days after start of treatment at the latest
Population: All participants who received at least one application of the BI drug BI 2536 (including treated patients who were not randomized) and for whom data were collected for this endpoint at the end-of-trial visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Change From Baseline in Pulse Rate at Individual Participant's End-of-trial Visit | 10.6 beats per minute (bpm) | Standard Deviation 14.3 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Change From Baseline in Pulse Rate at Individual Participant's End-of-trial Visit | 4.5 beats per minute (bpm) | Standard Deviation 13.3 |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Change From Baseline in Pulse Rate at Individual Participant's End-of-trial Visit | -8.0 beats per minute (bpm) | Standard Deviation 14.1 |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Change From Baseline in Pulse Rate at Individual Participant's End-of-trial Visit | 0.5 beats per minute (bpm) | Standard Deviation 14.4 |
Secondary
Change From Baseline in Systolic/Diastolic Blood Pressure at Individual Participant's End-of-trial Visit
Change from baseline in systolic/diastolic blood pressure at individual participant's end-of-trial visit.
Time frame: baseline, date of individual participant's end of trial visit which was 533 days after start of treatment at the latest
Population: All participants who received at least one application of the BI drug BI 2536 (including treated patients who were not randomized) and for whom data were collected for this endpoint at the end-of-trial visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Change From Baseline in Systolic/Diastolic Blood Pressure at Individual Participant's End-of-trial Visit | Change from baseline in systolic blood pressure | 2.4 millimetre of mercury (mmHg) | Standard Deviation 16.6 |
| 200 Milligram (mg) BI 2536 (Day 1) | Change From Baseline in Systolic/Diastolic Blood Pressure at Individual Participant's End-of-trial Visit | Change from baseline in diastolic blood pressure | -2.0 millimetre of mercury (mmHg) | Standard Deviation 14.7 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Change From Baseline in Systolic/Diastolic Blood Pressure at Individual Participant's End-of-trial Visit | Change from baseline in diastolic blood pressure | 0.8 millimetre of mercury (mmHg) | Standard Deviation 13.7 |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Change From Baseline in Systolic/Diastolic Blood Pressure at Individual Participant's End-of-trial Visit | Change from baseline in systolic blood pressure | -2.4 millimetre of mercury (mmHg) | Standard Deviation 14 |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Change From Baseline in Systolic/Diastolic Blood Pressure at Individual Participant's End-of-trial Visit | Change from baseline in systolic blood pressure | 2.9 millimetre of mercury (mmHg) | Standard Deviation 17.8 |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Change From Baseline in Systolic/Diastolic Blood Pressure at Individual Participant's End-of-trial Visit | Change from baseline in diastolic blood pressure | -7.1 millimetre of mercury (mmHg) | Standard Deviation 12.5 |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Change From Baseline in Systolic/Diastolic Blood Pressure at Individual Participant's End-of-trial Visit | Change from baseline in systolic blood pressure | -0.7 millimetre of mercury (mmHg) | Standard Deviation 15.1 |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Change From Baseline in Systolic/Diastolic Blood Pressure at Individual Participant's End-of-trial Visit | Change from baseline in diastolic blood pressure | -1.9 millimetre of mercury (mmHg) | Standard Deviation 13.5 |
Secondary
Duration of Overall Response
For participants who showed an overall tumour response of complete response (CR, disappearance of all target lesions) or partial response (PR, at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter), 'duration of overall response' was defined as the time from the first date where measurement criteria were met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease (PD) was objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started). Tumour response was evaluated based on local radiological images according to RECIST version 1.0 (agreed upon by independent review). The number of participants with an CR or PR who experienced the event 'recurrent or PD' is reported instead of the time-to-event data with unit of time as the number analyzed was too small to perform a Kaplan-Meier analysis.
Time frame: assessed at baseline, then every 6 weeks (every second treatment course) until disease progression or start of any other anti-tumour therapy or death or individual participant's end of trial, up to 533 days
Population: All participants who received at least one application of the BI drug BI 2536 (including treated participants who were not randomized) and who showed an 'overall tumour response of complete response or partial response'.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Duration of Overall Response | 2 Participants |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Duration of Overall Response | 0 Participants |
Secondary
Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades
Number of participants with adverse events categorized by common terminology criteria for adverse events (CTCAE) grades (version 3.0) are reported.
Time frame: On-treatment period, that is, from first administration of the trial drug until 3 weeks after the last administration of the trial drug, up to 428 days
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 4 | 14 Participants |
| 200 Milligram (mg) BI 2536 (Day 1) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 2 | 6 Participants |
| 200 Milligram (mg) BI 2536 (Day 1) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 5 | 6 Participants |
| 200 Milligram (mg) BI 2536 (Day 1) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 3 | 13 Participants |
| 200 Milligram (mg) BI 2536 (Day 1) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 1 | 7 Participants |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 3 | 8 Participants |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 4 | 4 Participants |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 5 | 1 Participants |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 2 | 7 Participants |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 1 | 6 Participants |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 3 | 7 Participants |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 1 | 2 Participants |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 2 | 2 Participants |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 4 | 6 Participants |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 5 | 4 Participants |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 4 | 10 Participants |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 2 | 9 Participants |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 1 | 8 Participants |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 3 | 15 Participants |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades | Grade 5 | 5 Participants |
Secondary
Incidence of Dose Limiting Toxicity (DLT)
Dose limiting toxicity was defined as drug related common terminology criteria for adverse events (CTCAE) grade 3 or greater non haematological toxicity (excluding untreated nausea, vomiting or diarrhoea) or drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection or CTCAE grade 4 thrombocytopenia. Number of participants with DLT is reported.
Time frame: On-treatment period, that is, from first administration of the trial drug until 3 weeks after the last administration of the trial drug, up to 428 days
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Incidence of Dose Limiting Toxicity (DLT) | 8 Participant |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Dose Limiting Toxicity (DLT) | 4 Participant |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Incidence of Dose Limiting Toxicity (DLT) | 3 Participant |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Incidence of Dose Limiting Toxicity (DLT) | 7 Participant |
Secondary
Number of Participants With Neutropenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4
Number of participants with neutropenia of common terminology criteria for adverse events (CTCAE) grade 3 or 4.
Time frame: On-treatment period, that is, from first administration of the trial drug until 3 weeks after the last administration of the trial drug, up to 428 days
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.~Participants with laboratory values that were out of range for CTCAE grading and were deemed possible clinically significant abnormal were excluded from the analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Number of Participants With Neutropenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 | 33 Number of Participants |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Number of Participants With Neutropenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 | 6 Number of Participants |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Number of Participants With Neutropenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 | 12 Number of Participants |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Number of Participants With Neutropenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 | 18 Number of Participants |
Secondary
Number of Participants With Thrombocytopenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4
Number of participants with thrombocytopenia of common terminology criteria for adverse events (CTCAE) grade 3 or 4.
Time frame: On-treatment period, that is, from first administration of the trial drug until 3 weeks after the last administration of the trial drug, up to 428 days
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.~Participants with laboratory values that were out of range for CTCAE grading and were deemed possible clinically significant abnormal were excluded from the analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Number of Participants With Thrombocytopenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 | 4 Number of Participants |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Number of Participants With Thrombocytopenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 | 1 Number of Participants |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Number of Participants With Thrombocytopenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 | 0 Number of Participants |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Number of Participants With Thrombocytopenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 | 1 Number of Participants |
Secondary
Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Investigator
The best overall response was the best response recorded from start of treatment until the participant progressed, received any other anti-tumour therapy, died or until the individual participant's end of trial. 'Objective tumour response evaluated according to RECIST 1.0 by investigator' is 'Yes' if the best overall response is either complete response (CR, disappearance of all target lesions) or partial response (PR, at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter). Otherwise it is 'No'. To be assigned a status of 'partial response' or 'complete response', changes in tumour measurements were confirmed by repeat assessments that had to be performed six weeks after the criteria for response had been first met. Number of participants with 'Objective tumour response evaluated according to RECIST 1.0 by investigator = Yes' are reported.
Time frame: assessed at baseline, then every 6 weeks (every second treatment course) until disease progression or start of any other anti-tumour therapy or death or individual participant's end of trial, up to 533 days
Population: All participants who received at least one application of the BI drug BI 2536 (including treated participants who were not randomized) and had at least one post-baseline response evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Investigator | 3 Number of Participants |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Investigator | 1 Number of Participants |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Investigator | 0 Number of Participants |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Investigator | 1 Number of Participants |
Secondary
Overall Survival
Overall survival defined as time from date of randomisation until date of death from any cause. Participants alive at the time of analysis were censored at the date of the last trial visit or last date of follow-up, whatever came last.
Time frame: every 6 weeks (every second treatment course), up to 599 days
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Overall Survival | 237 days |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Overall Survival | 244 days |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Overall Survival | 179 days |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Overall Survival | 196 days |
Comparison: Exploratory analysis. No formal hypotheses were tested.p-value: 0.6595% CI: [0.7, 1.78]Log Rank
Secondary
Progression Free Survival
Progression-free survival defined as time from date of randomisation until date of imaging indicating progressive disease (PD) as assessed by the independent central imaging review (according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0) or date of investigator assessment of clinical progression or date of progressive disease recorded during the follow-up period or death date, whatever comes first. Participants without documented progression at the time of analysis were censored at the date of the last visit. Per RECIST version 1.0 for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): PD, At least a 20% increase in the sum of the longest diameter (SoD) of target lesions taking as reference the smallest SoD of target lesions recorded since the treatment started or the appearance of one or more new lesions.
Time frame: every 6 weeks (every second treatment course), up to 419 days
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Progression Free Survival | 49 days |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Progression Free Survival | 51.5 days |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Progression Free Survival | 48 days |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Progression Free Survival | 49 days |
Comparison: Exploratory analysis. No formal hypotheses were tested.p-value: 0.9295% CI: [0.67, 1.55]Log Rank
Secondary
Time-to-deterioration for Symptom Score 'Cough' Assessed on Question 1 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0
Time to deterioration for cough \[days\] was defined as the time from randomization to deterioration in score for the symptom 'cough'. Participants were considered to have deteriorated if a 10-point increase from the baseline score at any time point after baseline was observed. Participants who died before deteriorating were analyzed as having deteriorated at the time of death. Participants with disease progression without deterioration in score were censored at the time of the last scale measurement. Participants with no QoL assessments were censored at day 1. The score for symptom 'cough' was based on Question 1 on the lung cancer module QLQ LC13 of the EORTC QLQ C30 Version 3.0. A linear transformation was used to standardize the raw scores, so that scores range from 0 to 100. A high score represents a higher (worse) level of the symptom 'cough'.
Time frame: baseline and every 3 weeks (prior to the first administration of BI 2536 in a treatment course comprising 3 weeks), up to 539 days
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Time-to-deterioration for Symptom Score 'Cough' Assessed on Question 1 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 108 days |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Time-to-deterioration for Symptom Score 'Cough' Assessed on Question 1 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 127 days |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Time-to-deterioration for Symptom Score 'Cough' Assessed on Question 1 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 99 days |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Time-to-deterioration for Symptom Score 'Cough' Assessed on Question 1 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 102 days |
95% CI: [0.94, 2.51]Regression, Cox
Secondary
Time-to-deterioration for Symptom Score 'Dyspnoea' Assessed on the Composite of Questions 3-5 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0
Time to deterioration for dyspnoea \[days\] was defined as the time from randomization to deterioration in score for the symptom 'dyspnoea'. Participants were considered to have deteriorated if a 10-point increase from the baseline score at any time point after baseline was observed. Participants who died before deteriorating were analyzed as having deteriorated at the time of death. Participants with disease progression without deterioration in score were censored at the time of the last scale measurement. Participants with no QoL assessments were censored at day 1. The score for symptom 'dyspnoea' was based on the composite of Questions 3-5 on the lung cancer module QLQ LC13 of the EORTC QLQ C30 Version 3.0. A linear transformation was used to standardize the raw scores, so that scores range from 0 to 100. A high score represents a higher (worse) level of the symptom 'dyspnoea'.
Time frame: baseline and every 3 weeks (prior to the first administration of BI 2536 in a treatment course comprising 3 weeks), up to 539 days
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Time-to-deterioration for Symptom Score 'Dyspnoea' Assessed on the Composite of Questions 3-5 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 56 days |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Time-to-deterioration for Symptom Score 'Dyspnoea' Assessed on the Composite of Questions 3-5 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 176 days |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Time-to-deterioration for Symptom Score 'Dyspnoea' Assessed on the Composite of Questions 3-5 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 80 days |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Time-to-deterioration for Symptom Score 'Dyspnoea' Assessed on the Composite of Questions 3-5 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 118 days |
95% CI: [0.59, 1.49]Regression, Cox
Secondary
Time-to-deterioration for Symptom Score 'Pain' Assessed on the Composite of Questions 9 and 19 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0
Time to deterioration for pain \[days\] was defined as the time from randomization to deterioration in score for the symptom 'pain'. Participants were considered to have deteriorated if a 10-point increase from the baseline score at any time point after baseline was observed. Participants who died before deteriorating were analyzed as having deteriorated at the time of death. Participants with disease progression without deterioration in score were censored at the time of the last scale measurement. Participants with no QoL assessments will be censored at day 1. The score for symptom 'pain' was based on the composite of Questions 9 and 19 of the EORTC QLQ C30 Version 3.0. A linear transformation was used to standardize the raw scores, so that scores range from 0 to 100. A high score represents a higher (worse) level of the symptom 'pain'.
Time frame: baseline and every 3 weeks (prior to the first administration of BI 2536 in a treatment course comprising 3 weeks), up to 539 days
Population: The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 200 Milligram (mg) BI 2536 (Day 1) | Time-to-deterioration for Symptom Score 'Pain' Assessed on the Composite of Questions 9 and 19 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 63 days |
| 50 Milligram BI 2536 (Day 1 - Day 3) | Time-to-deterioration for Symptom Score 'Pain' Assessed on the Composite of Questions 9 and 19 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 93 days |
| 60 Milligram BI 2536 (Day 1 - Day 3) | Time-to-deterioration for Symptom Score 'Pain' Assessed on the Composite of Questions 9 and 19 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 43 days |
| Combination of Treatment Group 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3) | Time-to-deterioration for Symptom Score 'Pain' Assessed on the Composite of Questions 9 and 19 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0 | 76 days |
95% CI: [0.81, 2.01]Regression, Cox