Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
The objective of the Phase I step is to estimate the MTD at a dose level up to 50 mg/day (i.e., overseas recommended Phase II dose) in patients with advanced NSCLC and to determine the recommended dose for the Phase II step. The objective of the Phase II step is to estimate the efficacy of BIBW 2992 monotherapy in patients with first generation EGFR-TKI-resistant advanced NSCLC at the recommended dose determined in the Phase I step.
Interventions
DRUGBIBW 2992 MA2 50mg/day
Phase I step: Increased dose cohorts from low dose to MTD
DRUGBIBW 2992 MA2 20mg/day
Phase I step: Increased dose cohorts from low dose to MTD
DRUGBIBW 2992 MA2 40mg/day
Phase I step: Increased dose cohorts from low dose to MTD
DRUGBIBW 2992 QD
Phase II step: This is an open label study. Patients are treated with BIBW 2992 until disease progression or undue AEs.
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase II step; 1. Patients with pathologic confirmation of NSCLC with tissue diagnosis or cytologic diagnosis, whose NSCLCs are locally advanced or metastatic Stage III-B / IV adenocarcinoma, and are inoperable and incurable with radiotherapy. 2. Patients who have received the following pretreatments for the treatment of relapsed or metastatic NSCLC. * Patients who have received at least one but not more than two lines of chemotherapy. (Chemotherapy means only the first line (doublet chemotherapies including a platinum) and/or the second line (single chemotherapy except for a platinum) of cytotoxic chemotherapy according to the standard chemotherapies, and erlotinib (Tarceva®) and gefitinib (Iressa®) should be excluded. One of the chemotherapy regimens must have been platinum-based. In addition, only one prior cytotoxic chemotherapy treatment regimen is allowed after adjuvant chemotherapy containing a platinum. More than two prior cytotoxic chemotherapy treatment regimens are not allowed.) * After the above chemotherapies, patients who once got clinical benefits (i.e. complete response, partial response or stable disease) but progressed following at least 12 weeks of treatment with erlotinib (Tarceva®) or gefitinib (Iressa®) as the most recent treatment. (Clinical benefit and progression should be confirmed by computed tomography (CT) or magnetic resonance imaging (MRI). In addition, at least 12 weeks of treatment should be 9 weeks or more as the actual treatment period except for treatment pause due to adverse events and other reasons.) As long as the treatment is erlotinib or gefitinib monotherapy, patients can receive multiple regimens of either or both treatments, but one of the regimens should be for at least 12 weeks 3. Male or female patients age \>=20 years at the enrolment. 4. Life expectancy of at least three (3) months after the start of administration of the investigational drug. 5. Eastern Cooperative Oncology Group (ECOG) performance Score 0 or 1. 6. Patients with at least one tumor lesion that can accurately be measured by CT or MRI in at least one dimension with longest diameter to be recorded as no less than double the slice thickness and \>=10 mm. 7. Written informed consent that is consistent with ICH-GCP guidelines.
Exclusion criteria
Phase II step; 1. Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within two weeks before starting the study medication. 2. Patients who have received definitive thoracic radiotherapy with curative intent. Patients who have received radiotherapy or other investigational drugs (non-oncological) within four weeks before enrolment. 3. Significant gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn's disease, mal-absorption, or CTCAE Grade \>2 diarrhea of any etiology at the enrolment. 4. Patients with distinct / suspected pulmonary fibrosis or interstitial lung disease by the chest radiographic findings, or patients with a previous history of. 5. Brain tumor, and / or brain metastases, which are symptomatic or requiring treatment at the enrolment. 6. Other malignancies diagnosed within the past five years (other than carcinoma in situ of gastric cancer, colon cancer and cervical cancer, and non melanomatous skin cancer). 7. History of uncontrolled cardiac disease such as angina or myocardial infarction within the past 6 months at the enrolment, congestive heart failure including New York Heart Association (NYHA) functional classification of 3, or arrhythmia requiring treatment. 8. Coelomic fluid retention (such as pleural effusion, ascites or pericardial effusion) requiring treatment. 9. Uncontrolled concomitant diseases (e.g. diabetes mellitus, hypertension etc). 10. History of serious drug hypersensitivity. 11. Patients who do not have sufficient baseline organ function and whose laboratory data do not meet the following criteria at the enrolment.11 * Haemoglobin count \>=9.0 g/dL * Absolute neutrophil count (ANC) \>=1500 / mm3 * Platelet count \>=100 000 / mm3 * Serum creatinine \<=1.5 mg/dL * Total bilirubin \<=1.5 mg/dL * Aspartate aminotransferase (AST) and / or alanine aminotransferase (ALT) \<=2.5x upper limit of normal range (if related to liver metastases \<=2.5x upper limit of normal also) * PaO2 \>=60torr or SpO2 \>=92% * LVEF as measured by echocardiography or multigated blood pool imaging of the heart (MUGA scan) \>=50% * QTc interval \<0.47 second 12. Patients who disagree with using a medically acceptable method of contraception during the administration of the investigational drug and for at least 6 months after the end of administration. 13. Pregnant or breast-feeding women, or women suspected of being pregnant. 14. Known positive HBs antigen, HCV antibody, or HIV antibody test. 15. Known or suspected active drug or alcohol abuse. 16. Other patients judged ineligible for enrolment in the study by the investigator (sub-investigator).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | start of treatment to end of treatment | — |
| Phase II Step: Objective Tumour Response According to Response Evaluation Criteria in Solid Tumours (RECIST) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration | 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 | 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. |
| Phase II Step: Clinical Benefit | 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 | 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. |
| Phase II Step: Time to Objective Response | 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 | Number of participants with first response at week 4, 8 and 12, assessed by investigator and independent review. |
| Phase II Step: Duration of Objective Response | 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 | 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. |
| Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | Screening visit | — |
| Phase II Step: Duration of Clinical Benefit | 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 | Presented as duration of disease control. |
| Phase II Step: Progression-free Survival (PFS) | 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 | 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. |
| Phase II Step: Overall Survival (OS) | 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. |
| Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE | Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up | outcome data show the number of patients with Adverse events (AE) by intensity and incidence of adverse events, graded according to CTCAE. |
| Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline | Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up | 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 |
| Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course1 Day 15 | Course 1 Day 15 | 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. |
| Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 1 | Course 2 Day 1 | Outcome data show the gMean of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW |
| Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 15 | Course 2 Day 15 | Outcome data show the gMean of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW |
| Phase II Step: Summary of EGFR Mutation Findings | Screening visit | — |
| Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration | Just before start of the treatment to Course 4 Visit 4R2 | — |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BIBW 20mg Continuous once daily oral treatment with BIBW 2992 20mg tablets | 3 |
| BIBW 40mg Continuous once daily oral treatment with BIBW 2992 40mg tablets | 3 |
| BIBW 50mg (Phase I) Continuous once daily oral treatment with BIBW 2992 50mg tablets | 6 |
| BIBW 50mg (Phase II) Continuous once daily oral treatment with BIBW 2992 50mg tablets | 62 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Other Adverse Event | 1 | 0 | 0 | 16 |
| Overall Study | Progressive disease | 2 | 2 | 6 | 44 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | BIBW 20mg | BIBW 40mg | BIBW 50mg (Phase I) | BIBW 50mg (Phase II) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 65.0 years | 56.0 years | 63.0 years | 65.0 years | 65.0 years |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 3 Participants | 48 Participants | 55 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 3 Participants | 14 Participants | 19 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 | 62 / 62 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 2 / 6 | 16 / 62 |
Outcome results
Primary
Phase II Step: Objective Tumour Response According to Response Evaluation Criteria in Solid Tumours (RECIST)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBW 20mg | Phase II Step: Objective Tumour Response According to Response Evaluation Criteria in Solid Tumours (RECIST) | Independent review | 8.2 percentage of participants |
| BIBW 20mg | Phase II Step: Objective Tumour Response According to Response Evaluation Criteria in Solid Tumours (RECIST) | Investigator assessment | 13.1 percentage of participants |
Primary
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
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 40mg | 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 |
| BIBW 40mg | 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 |
| BIBW 40mg | 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 |
| BIBW 40mg | 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) | 1 participants |
| BIBW 40mg | 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 | 0 participants |
| BIBW 40mg | 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 | 0 participants |
| BIBW 40mg | 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 |
| BIBW 40mg | 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 | 0 participants |
| BIBW 40mg | 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 | 0 participants |
| BIBW 40mg | 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 |
| BIBW 40mg | 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) | 3 participants |
| BIBW 40mg | 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) | 0 participants |
| BIBW 40mg | 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 |
| BIBW 40mg | 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 |
| BIBW 40mg | 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 |
| BIBW 50mg (Phase I) | 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) | 1 participants |
| BIBW 50mg (Phase I) | 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) | 3 participants |
| BIBW 50mg (Phase I) | 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 | 1 participants |
| BIBW 50mg (Phase I) | 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) | 3 participants |
| BIBW 50mg (Phase I) | 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 |
| BIBW 50mg (Phase I) | 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 | 2 participants |
| BIBW 50mg (Phase I) | 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 | 6 participants |
| BIBW 50mg (Phase I) | 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 |
| BIBW 50mg (Phase I) | 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 | 0 participants |
| BIBW 50mg (Phase I) | 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 | 6 participants |
| BIBW 50mg (Phase I) | 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) | 1 participants |
| BIBW 50mg (Phase I) | 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 | 0 participants |
| BIBW 50mg (Phase I) | 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) | 1 participants |
| BIBW 50mg (Phase I) | 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) | 2 participants |
| BIBW 50mg (Phase I) | 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 |
Secondary
Phase II Step: Clinical Benefit
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.
Time frame: 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 includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBW 20mg | Phase II Step: Clinical Benefit | Independent review | 65.6 percentage of participants |
| BIBW 20mg | Phase II Step: Clinical Benefit | Investigator assessment | 72.1 percentage of participants |
Secondary
Phase II Step: Duration of Clinical Benefit
Presented as duration of disease control.
Time frame: 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 includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BIBW 20mg | Phase II Step: Duration of Clinical Benefit | Independent review | 19.9 Weeks |
| BIBW 20mg | Phase II Step: Duration of Clinical Benefit | Investigator assessment | 20.9 Weeks |
Secondary
Phase II Step: Duration of Objective Response
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.
Time frame: 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 includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BIBW 20mg | Phase II Step: Duration of Objective Response | Independent review | 19.9 weeks |
| BIBW 20mg | Phase II Step: Duration of Objective Response | Investigator assessment | 16.1 weeks |
Secondary
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline
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
Time frame: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
Secondary
Phase II Step: Overall Survival (OS)
OS was defined as the duration of time from the start of treatment to the time of death.
Time frame: from start of treatment until end of follow up, up to 53 months
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BIBW 20mg | Phase II Step: Overall Survival (OS) | 18.4 Months |
Secondary
Phase II Step: Progression-free Survival (PFS)
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.
Time frame: 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 includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BIBW 20mg | Phase II Step: Progression-free Survival (PFS) | Independent review | 4.5 Months |
| BIBW 20mg | Phase II Step: Progression-free Survival (PFS) | Investigator assessment | 4.6 Months |
Secondary
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE
outcome data show the number of patients with Adverse events (AE) by intensity and incidence of adverse events, graded according to CTCAE.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE | Serious AEs | 16 participants |
| BIBW 20mg | Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE | SAE: Fatal | 1 participants |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE | SAE: Other | 1 participants |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 20mg | 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
Phase II Step: Summary of EGFR Mutation Findings
Time frame: Screening visit
Population: The treated set of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBW 20mg | Phase II Step: Summary of EGFR Mutation Findings | EGFR Mutation test done (local or central) | 56 participants |
| BIBW 20mg | Phase II Step: Summary of EGFR Mutation Findings | Negative | 11 participants |
| BIBW 20mg | Phase II Step: Summary of EGFR Mutation Findings | Positive | 45 participants |
| BIBW 20mg | Phase II Step: Summary of EGFR Mutation Findings | Del19 | 22 participants |
| BIBW 20mg | Phase II Step: Summary of EGFR Mutation Findings | Del19 + L858R | 1 participants |
| BIBW 20mg | Phase II Step: Summary of EGFR Mutation Findings | Del19 + T790M | 1 participants |
| BIBW 20mg | Phase II Step: Summary of EGFR Mutation Findings | Del19 + Other | 1 participants |
| BIBW 20mg | Phase II Step: Summary of EGFR Mutation Findings | L858R | 15 participants |
| BIBW 20mg | Phase II Step: Summary of EGFR Mutation Findings | L858R + T790M | 1 participants |
| BIBW 20mg | Phase II Step: Summary of EGFR Mutation Findings | L858R + Other | 3 participants |
| BIBW 20mg | Phase II Step: Summary of EGFR Mutation Findings | L861Q | 1 participants |
Secondary
Phase II Step: Time to Objective Response
Number of participants with first response at week 4, 8 and 12, assessed by investigator and independent review.
Time frame: 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 includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBW 20mg | Phase II Step: Time to Objective Response | Time to first response (Week4, Independent) | 4 Number of patients |
| BIBW 20mg | Phase II Step: Time to Objective Response | Time to first response (Week8, Investigator) | 2 Number of patients |
| BIBW 20mg | Phase II Step: Time to Objective Response | Time to first response (Week12, Investigator) | 1 Number of patients |
| BIBW 20mg | Phase II Step: Time to Objective Response | Time to first response (Week8, Independent) | 1 Number of patients |
| BIBW 20mg | Phase II Step: Time to Objective Response | Time to first response (Week12, Independent) | 0 Number of patients |
| BIBW 20mg | Phase II Step: Time to Objective Response | Time to first response (Week4, Investigator) | 5 Number of patients |
Secondary
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course1 Day 15
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BIBW 40mg | 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 |
| BIBW 50mg (Phase I) | Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course1 Day 15 | 44.0 ng/ml | Geometric Coefficient of Variation 60 |
Secondary
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 1
Outcome data show the gMean of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BIBW 20mg | 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 |
| BIBW 40mg | Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 1 | 29.8 ng/ml | Geometric Coefficient of Variation 47.8 |
| BIBW 50mg (Phase I) | Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 1 | 38.3 ng/ml | Geometric Coefficient of Variation 71.2 |
Secondary
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 15
Outcome data show the gMean of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW
Time frame: Course 2 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.~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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BIBW 20mg | 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 |
| BIBW 40mg | Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 15 | 32.1 ng/ml | Geometric Coefficient of Variation 52.5 |
| BIBW 50mg (Phase I) | Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 15 | 28.6 ng/ml | Geometric Coefficient of Variation 138 |
Secondary
Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration
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.
Time frame: 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)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BIBW 20mg | 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 |
| BIBW 20mg | 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 |
| BIBW 40mg | Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration | AUC0-24 | 299 ng·h/mL | Geometric Coefficient of Variation 6.01 |
| BIBW 40mg | Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration | AUCtau,ss | 1240 ng·h/mL | Geometric Coefficient of Variation 9.73 |
| BIBW 50mg (Phase I) | Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration | AUC0-24 | 539 ng·h/mL | Geometric Coefficient of Variation 59 |
| BIBW 50mg (Phase I) | Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration | AUCtau,ss | 1010 ng·h/mL | Geometric Coefficient of Variation 71.5 |
Secondary
Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration
Time frame: 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
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BIBW 20mg | Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration | Cmax | 12.4 ng/mL | Geometric Coefficient of Variation 101 |
| BIBW 20mg | 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 |
| BIBW 40mg | Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration | Cmax | 18.9 ng/mL | Geometric Coefficient of Variation 45.8 |
| BIBW 40mg | Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration | Cmax,ss | 83.3 ng/mL | Geometric Coefficient of Variation 30.1 |
| BIBW 50mg (Phase I) | Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration | Cmax | 44.4 ng/mL | Geometric Coefficient of Variation 60.6 |
| BIBW 50mg (Phase I) | Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration | Cmax,ss | 66.8 ng/mL | Geometric Coefficient of Variation 71.6 |
Secondary
Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings
Time frame: Screening visit
Population: The treated set of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIBW 20mg | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | Patients with positive EGFR mutation status | 2 participants |
| BIBW 20mg | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | Del19 + T790M | 2 participants |
| BIBW 20mg | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | L858R + T790M | 0 participants |
| BIBW 20mg | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | S768I | 0 participants |
| BIBW 40mg | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | S768I | 1 participants |
| BIBW 40mg | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | Patients with positive EGFR mutation status | 1 participants |
| BIBW 40mg | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | L858R + T790M | 0 participants |
| BIBW 40mg | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | Del19 + T790M | 0 participants |
| BIBW 50mg (Phase I) | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | S768I | 0 participants |
| BIBW 50mg (Phase I) | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | Del19 + T790M | 1 participants |
| BIBW 50mg (Phase I) | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | L858R + T790M | 1 participants |
| BIBW 50mg (Phase I) | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | Patients with positive EGFR mutation status | 2 participants |