Trial Outcomes & Findings for LUX-Lung 4: BIBW 2992 (Afatinib) Phase I Trial in Advanced Non Small Cell Lung Cancer Patients & Phase II Trial in Non Small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (NCT NCT00711594)

NCT ID: NCT00711594

Last Updated: 2015-01-15

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

74 participants

Primary outcome timeframe

start of treatment to end of treatment

Results posted on

2015-01-15

Participant Flow

Participant milestones

Participant milestones
Measure	BIBW 20mg Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets	BIBW 50mg (Phase II) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Overall Study STARTED	3	3	6	62
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	3	3	6	62

Reasons for withdrawal

Reasons for withdrawal
Measure	BIBW 20mg Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets	BIBW 50mg (Phase II) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Overall Study Progressive disease	2	2	6	44
Overall Study Other Adverse Event	1	0	0	16
Overall Study Withdrawal by Subject	0	1	0	2

Baseline Characteristics

LUX-Lung 4: BIBW 2992 (Afatinib) Phase I Trial in Advanced Non Small Cell Lung Cancer Patients & Phase II Trial in Non Small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BIBW 20mg n=3 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg n=3 Participants Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) n=6 Participants Continuous once daily oral treatment with BIBW 2992 50mg tablets	BIBW 50mg (Phase II) n=62 Participants Continuous once daily oral treatment with BIBW 2992 50mg tablets	Total n=74 Participants Total of all reporting groups
Age, Continuous	65.0 years n=5 Participants	56.0 years n=7 Participants	63.0 years n=5 Participants	65.0 years n=4 Participants	65.0 years n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	48 Participants n=4 Participants	55 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	14 Participants n=4 Participants	19 Participants n=21 Participants

PRIMARY outcome

Timeframe: start of treatment to end of treatment

Population: The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=3 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg n=3 Participants Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) n=6 Participants Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE Patients with any AE	3 participants	3 participants	6 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE Investigator defined drug-related AEs	3 participants	3 participants	6 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE Other significant AEs (according to ICH E3)	0 participants	1 participants	1 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE AEs leading to discontinuation of trial drug	1 participants	0 participants	0 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE Serious AEs	1 participants	0 participants	2 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE SAE: Requiring hospitalisation	0 participants	0 participants	1 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE SAE: Prolonging hospitalisation	1 participants	0 participants	1 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE SAE: Other	1 participants	0 participants	0 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE Highest CTCAE grade for AEs (Grade 1)	0 participants	0 participants	1 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE Highest CTCAE grade for AEs (Grade 2)	1 participants	3 participants	2 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE Highest CTCAE grade for AEs (Grade 4)	0 participants	0 participants	0 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE Highest CTCAE grade for AEs (Grade 5)	0 participants	0 participants	0 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE Patients with any DLT (Course 1)	0 participants	0 participants	1 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE Patients with any DLT (All Courses)	0 participants	0 participants	3 participants
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE Highest CTCAE grade for AEs (Grade 3)	2 participants	0 participants	3 participants

PRIMARY outcome

Timeframe: Tumour Assessment were performed at screening 14 days (prior to enrollment), in week 4, week 8, week 12 and in 8-week intervals thereafter, and at the end of trial visit (patients discontinuation), up to 41.3 months

Population: The "full analysis set" of patients was defined as all patients included in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started.

The objective response (complete response \[CR\] and partial response \[PR\]) was defined as determined by the RECIST according to the best response to study treatment.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=61 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Objective Tumour Response According to Response Evaluation Criteria in Solid Tumours (RECIST) Independent review	8.2 percentage of participants Interval 2.7 to 18.1	—	—
Phase II Step: Objective Tumour Response According to Response Evaluation Criteria in Solid Tumours (RECIST) Investigator assessment	13.1 percentage of participants Interval 5.8 to 24.2	—	—

SECONDARY outcome

Timeframe: AUC0-24: just before drug administration, 0:30,1:00, 2:00, 3:00, 4:00, 5:00, 7:00, 9:00, 24:00 on Day 1-2 in Course 1; AUCtau,ss: just before drug administration, 0:30,1:00, 2:00, 3:00, 4:00, 5:00, 7:00, 9:00, 24:00, 48:00, 72:00 on Day 28-31 in Course 1

Population: "Treated set" was defined as all patients who received at least 1 dose of BIBW2992. Some samples were excluded from calculation of descriptive statistics of plasma concentration because these were taken outside the allowed time-windows but used for calculation of PK parameters. Number of analyzed patients of BIBW 50mg:5(AUCtau,ss), 40mg:2(AUC0-24)

area under the concentration-time curve of BIBW 2992 over the time interval 0-24 hours (AUC0-24), Area under the concentration-time curve of Afatinib in plasma at steady state (AUCtau,ss) after multiple oral administration Pharmacokinetic was abbreviated to PK.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=3 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg n=3 Participants Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) n=6 Participants Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration AUC0-24	147 ng·h/mL Geometric Coefficient of Variation 84.5	299 ng·h/mL Geometric Coefficient of Variation 6.01	539 ng·h/mL Geometric Coefficient of Variation 59.0
Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration AUCtau,ss	409 ng·h/mL Geometric Coefficient of Variation 16.5	1240 ng·h/mL Geometric Coefficient of Variation 9.73	1010 ng·h/mL Geometric Coefficient of Variation 71.5

SECONDARY outcome

Population: The "full analysis set" of patients was defined as all patients includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started.

Clinical benefit was defined as a RECIST assessment of complete response, partial response, or stable disease according to the best response to study treatment as defined in the previous section. Clinical benefit presented as the disease control.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=61 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Clinical Benefit Independent review	65.6 percentage of participants Interval 52.3 to 77.3	—	—
Phase II Step: Clinical Benefit Investigator assessment	72.1 percentage of participants Interval 59.2 to 82.9	—	—

SECONDARY outcome

Number of participants with first response at week 4, 8 and 12, assessed by investigator and independent review.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=61 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Time to Objective Response Time to first response (Week8, Independent)	1 Number of patients	—	—
Phase II Step: Time to Objective Response Time to first response (Week12, Independent)	0 Number of patients	—	—
Phase II Step: Time to Objective Response Time to first response (Week4, Investigator)	5 Number of patients	—	—
Phase II Step: Time to Objective Response Time to first response (Week8, Investigator)	2 Number of patients	—	—
Phase II Step: Time to Objective Response Time to first response (Week12, Investigator)	1 Number of patients	—	—
Phase II Step: Time to Objective Response Time to first response (Week4, Independent)	4 Number of patients	—	—

SECONDARY outcome

Duration of objective response was defined as the time at which RECIST was first met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease (PD) was objectively documented.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=61 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Duration of Objective Response Independent review	19.9 weeks Interval 6.9 to 112.1	—	—
Phase II Step: Duration of Objective Response Investigator assessment	16.1 weeks Interval 12.1 to 28.4	—	—

SECONDARY outcome

Timeframe: Screening visit

Population: The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=2 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg n=3 Participants Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) n=6 Participants Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings Patients with positive EGFR mutation status	2 participants	1 participants	2 participants
Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings Del19 + T790M	2 participants	0 participants	1 participants
Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings L858R + T790M	0 participants	0 participants	1 participants
Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings S768I	0 participants	1 participants	0 participants

SECONDARY outcome

Presented as duration of disease control.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=61 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Duration of Clinical Benefit Independent review	19.9 Weeks Interval 7.7 to 116.4	—	—
Phase II Step: Duration of Clinical Benefit Investigator assessment	20.9 Weeks Interval 10.1 to 180.4	—	—

SECONDARY outcome

PFS was defined as the duration of time from the start of treatment until the day of objective tumour progression confirmed by tumour imaging (PD according to the RECIST) or death.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=61 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Progression-free Survival (PFS) Independent review	4.5 Months Interval 1.9 to 6.0	—	—
Phase II Step: Progression-free Survival (PFS) Investigator assessment	4.6 Months Interval 2.8 to 10.0	—	—

SECONDARY outcome

Timeframe: from start of treatment until end of follow up, up to 53 months

OS was defined as the duration of time from the start of treatment to the time of death.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=61 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Overall Survival (OS)	18.4 Months Interval 11.9 to 36.3	—	—

SECONDARY outcome

Timeframe: Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up

Population: The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication.

outcome data show the number of patients with Adverse events (AE) by intensity and incidence of adverse events, graded according to CTCAE.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=62 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE Patients with any AE	62 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE Investigator defined drug-related AEs	62 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE AEs leading to dose reduction of trial drug	43 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE AEs leading to discontinuation of trial drug	19 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE Serious AEs	16 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE SAE: Fatal	1 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE SAE: Immediate life-threatening	1 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE SAE: Requiring hospitalisation	13 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE SAE: Prolonging hospitalisation	4 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE SAE: Other	1 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE Highest CTCAE grade for AEs (Grade 1)	0 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE Highest CTCAE grade for AEs (Grade 2)	11 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE Highest CTCAE grade for AEs (Grade 3)	48 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE Highest CTCAE grade for AEs (Grade 4)	2 participants	—	—
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE Highest CTCAE grade for AEs (Grade 5)	1 participants	—	—

SECONDARY outcome

Timeframe: Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up

Population: The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication. For activated partial thromboplastin time (APTT), N = 59 For Prothrombin Time and International Normalized Ratio (PT-INR), N = 61

outcome data show the number of patients for the maximum CTC grade during the trial for laboratory parameters, among patients who experienced an increase in CTC Grade

Outcome measures

Outcome measures
Measure	BIBW 20mg n=62 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline White blood cell count (CTCAE Grade1)	5 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline White blood cell count (CTCAE Grade2)	6 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline White blood cell count (CTCAE Grade3)	1 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline White blood cell count (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline White blood cell count (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Haemoglobin (CTCAE Grade1)	21 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Haemoglobin (CTCAE Grade2)	7 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Haemoglobin (CTCAE Grade3)	1 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Haemoglobin (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Haemoglobin (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Platelets (CTCAE Grade1)	4 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Platelets (CTCAE Grade2)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Platelets (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Platelets (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Platelets (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Neutrophils (CTCAE Grade1)	20 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Neutrophils (CTCAE Grade2)	5 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Neutrophils (CTCAE Grade3)	1 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Neutrophils (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Neutrophils (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Lymphocytes (CTCAE Grade1)	27 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Lymphocytes (CTCAE Grade2)	7 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Lymphocytes (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline APTT (CTCAE Grade1)	1 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline APTT (CTCAE Grade2)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline APTT (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline APTT (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline APTT (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline PT-INR (CTCAE Grade1)	5 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline PT-INR (CTCAE Grade2)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline PT-INR (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline PT-INR (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline PT-INR (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypocalcaemia (CTCAE Grade1)	16 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypocalcaemia (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypocalcaemia (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypernatraemia (CTCAE Grade1)	1 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypernatraemia (CTCAE Grade2)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypernatraemia (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypernatraemia (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypernatraemia (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyponatraemia (CTCAE Grade1)	14 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyponatraemia (CTCAE Grade2)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyponatraemia (CTCAE Grade3)	1 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyponatraemia (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline AST/GOT, SGOT (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline AST/GOT, SGOT (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline AST/GOT, SGOT (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline ALT/GPT, SGPT (CTCAE Grade1)	8 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline ALT/GPT, SGPT (CTCAE Grade2)	7 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline ALT/GPT, SGPT (CTCAE Grade3)	1 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline ALT/GPT, SGPT (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline ALT/GPT, SGPT (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Alkaline phosphatase (CTCAE Grade1)	14 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Alkaline phosphatase (CTCAE Grade2)	1 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Alkaline phosphatase (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Creatine phosphatase (CTCAE Grade1)	9 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Creatine phosphatase (CTCAE Grade2)	4 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Creatine phosphatase (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Creatine phosphatase (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Creatine phosphatase (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Albumin (CTCAE Grade1)	31 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Uric acid (CTCAE Grade1)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Uric acid (CTCAE Grade2)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Uric acid (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Uric acid (CTCAE Grade4)	2 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Uric acid (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Bilirubin, total (CTCAE Grade1)	4 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Bilirubin, total (CTCAE Grade2)	2 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Bilirubin, total (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Bilirubin, total (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Bilirubin, total (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyperglycaem (CTCAE Grade1)	23 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyperglycaem (CTCAE Grade2)	5 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyperglycaem (CTCAE Grade3)	1 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyperglycaem (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyperglycaem (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypoglycaemia (CTCAE Grade1)	2 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypoglycaemia (CTCAE Grade2)	1 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypoglycaemia (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypoglycaemia (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypoglycaemia (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline U. protein (qual) (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline U. protein (qual) (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline U. protein (qual) (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Lymphocytes (CTCAE Grade3)	6 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Lymphocytes (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypocalcaemia (CTCAE Grade2)	4 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypocalcaemia (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyponatraemia (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyperkalemia (CTCAE Grade1)	8 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyperkalemia (CTCAE Grade2)	2 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyperkalemia (CTCAE Grade3)	1 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyperkalemia (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hyperkalemia (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypokalemia (CTCAE Grade1)	18 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypokalemia (CTCAE Grade2)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypokalemia (CTCAE Grade3)	2 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypokalemia (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Hypokalemia (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline AST/GOT, SGOT (CTCAE Grade1)	12 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline AST/GOT, SGOT (CTCAE Grade2)	4 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Alkaline phosphatase (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Alkaline phosphatase (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Albumin (CTCAE Grade2)	6 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Albumin (CTCAE Grade3)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Albumin (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Albumin (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Creatinine (CTCAE Grade1)	13 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Creatinine (CTCAE Grade2)	5 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Creatinine (CTCAE Grade3)	2 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Creatinine (CTCAE Grade4)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline Creatinine (CTCAE Grade5)	0 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline U. protein (qual) (CTCAE Grade1)	20 participants	—	—
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline U. protein (qual) (CTCAE Grade2)	6 participants	—	—

SECONDARY outcome

Timeframe: Course 1 Day 15

Population: Plasma concentrations of BIBW2992 were to be presented for all patients and sampling points with concentrations above the lower limit of quantification. No patient was treated with 30 mg during the Course 1.

Outcome data show the geometric mean (gMean) of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW. The dose determined from the result of the Phase I step (50 mg) will be used. Reduction of dose in accordance to the criteria specified by adverse events to 40 mg or 30 mg was possible.

Outcome measures

Outcome measures
Measure	BIBW 20mg Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg n=5 Participants Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) n=49 Participants Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course1 Day 15	—	28.6 ng/ml Geometric Coefficient of Variation 33.2	44.0 ng/ml Geometric Coefficient of Variation 60.0

SECONDARY outcome

Timeframe: Course 2 Day 1

Population: Plasma concentrations of BIBW2992 were to be presented for all patients and sampling points with concentrations above the lower limit of quantification. The dose determined from the result of the Phase I step (50 mg) will be used. Reduction of dose in accordance to the criteria specified by adverse events to 40 mg or 30 mg was possible.

Outcome data show the gMean of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW

Outcome measures

Outcome measures
Measure	BIBW 20mg n=2 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg n=14 Participants Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) n=26 Participants Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 1	27.2 ng/ml Geometric Coefficient of Variation 0.259	29.8 ng/ml Geometric Coefficient of Variation 47.8	38.3 ng/ml Geometric Coefficient of Variation 71.2

SECONDARY outcome

Timeframe: Course 2 Day 15

Outcome data show the gMean of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW

Outcome measures

Outcome measures
Measure	BIBW 20mg n=5 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg n=18 Participants Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) n=16 Participants Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 15	30.1 ng/ml Geometric Coefficient of Variation 24.8	32.1 ng/ml Geometric Coefficient of Variation 52.5	28.6 ng/ml Geometric Coefficient of Variation 138

SECONDARY outcome

Timeframe: Screening visit

Population: The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication.

Outcome measures

Outcome measures
Measure	BIBW 20mg n=62 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase II Step: Summary of EGFR Mutation Findings EGFR Mutation test done (local or central)	56 participants	—	—
Phase II Step: Summary of EGFR Mutation Findings Positive	45 participants	—	—
Phase II Step: Summary of EGFR Mutation Findings Del19	22 participants	—	—
Phase II Step: Summary of EGFR Mutation Findings Del19 + L858R	1 participants	—	—
Phase II Step: Summary of EGFR Mutation Findings Del19 + T790M	1 participants	—	—
Phase II Step: Summary of EGFR Mutation Findings Del19 + Other	1 participants	—	—
Phase II Step: Summary of EGFR Mutation Findings L858R	15 participants	—	—
Phase II Step: Summary of EGFR Mutation Findings L858R + T790M	1 participants	—	—
Phase II Step: Summary of EGFR Mutation Findings L858R + Other	3 participants	—	—
Phase II Step: Summary of EGFR Mutation Findings L861Q	1 participants	—	—
Phase II Step: Summary of EGFR Mutation Findings Negative	11 participants	—	—

SECONDARY outcome

Timeframe: Just before start of the treatment to Course 4 Visit 4R2

Population: The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication.Some samples were excluded from the evaluation because these were taken outside the allowed time-windows. Number of analyzed patients of BIBW 50mg cohort for Cmax,ss: 5

Outcome measures

Outcome measures
Measure	BIBW 20mg n=3 Participants Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg n=3 Participants Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) n=6 Participants Continuous once daily oral treatment with BIBW 2992 50mg tablets
Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration Cmax	12.4 ng/mL Geometric Coefficient of Variation 101	18.9 ng/mL Geometric Coefficient of Variation 45.8	44.4 ng/mL Geometric Coefficient of Variation 60.6
Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration Cmax,ss	26.9 ng/mL Geometric Coefficient of Variation 24.9	83.3 ng/mL Geometric Coefficient of Variation 30.1	66.8 ng/mL Geometric Coefficient of Variation 71.6

Adverse Events

BIBW 20mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

BIBW 40mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

BIBW 50mg (Phase I)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

BIBW 50mg (Phase II)

Serious events: 16 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	BIBW 20mg n=3 participants at risk Continuous once daily oral treatment with BIBW 2992 20mg tablets	BIBW 40mg n=3 participants at risk Continuous once daily oral treatment with BIBW 2992 40mg tablets	BIBW 50mg (Phase I) n=6 participants at risk Continuous once daily oral treatment with BIBW 2992 50mg tablets	BIBW 50mg (Phase II) n=62 participants at risk Continuous once daily oral treatment with BIBW 2992 50mg tablets
Infections and infestations Bronchitis	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Infections and infestations Pneumonia bacterial	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Infections and infestations Sepsis	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bile duct cancer	33.3% 1/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	3.2% 2/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Nervous system disorders Syncope	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	6.5% 4/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Gastrointestinal disorders Enteritis	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	16.7% 1/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Gastrointestinal disorders Ileus	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Hepatobiliary disorders Cholecystitis	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Renal and urinary disorders Renal failure acute	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
General disorders Fatigue	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
General disorders Mucosal inflammation	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	16.7% 1/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Investigations Blood creatinine increased	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Injury, poisoning and procedural complications Bone contusion	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/3 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	0.00% 0/6 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days	1.6% 1/62 • from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days