Locally advanced or metastatic non-small cell lung cancer (NSCLC) MedDRA version: 19.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: BI 1482694
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not assigned yet
CAS Number: 1353550-13-6
Current Sponsor code: BI 1482694
Concentration unit: mg milligram(s)
Con
Sponsors
Boehringer Ingelheim International GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Pathologically confirmed diagnosis of adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology. 2. Locally Advanced Stage IIIb or metastatic stage IV NSCLC. 3. At least one documented EGFR mutation known to be associated with EGFR TKI sensitivity e.g. exon 19 deletion, L858R, L861Q, G719X. 4. Presence of T790M mutation confirmed by central laboratory analysis of tumor tissue obtained after disease progression on, or after first-line treatment with an approved EGFR-TKI. 5. Radiologically confirmed progression or recurrence of disease during or following first-line treatment with an approved 1st or 2nd generation EGFR -TKI. 6. At least one target lesion (excluding the brain), that can be accurately measured per RECIST version 1.1. 7. Eligible to receive treatment with the selected doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/ pemetrexed) in accordance with SmPC/PI. 8. Patients aged at least 18 years or over the legal age of consent in countries where that is greater than 18 years. 9. Eastern Cooperative Oncology Group (ECOG) score: 0 or 1 (R01-0787). 10. Adequate organ function. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 420 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 280
Exclusion criteria
Exclusion criteria: 1. More than one line of prior therapy for locally advanced stage IIIb or metastatic stage IV NSCLC. a. Radiotherapy alone is not counted as a line of therapy; b. Radiosensitisers and/or intrapleural administration of anti-cancer agents are not counted as a line of therapy. 2. Previous treatment with BI 1482694, or other 3rd generation EGFR inhibiting drugs that target T790M-positive mutant EGFR (e.g. AZD9291, CO-1686). 3. Previous treatment with an approved 1st or 2nd generation EGFR-TKI i.e. erlotinib, gefitinib, and afatinib within 8 days or 5 half-lives, whichever is longer, prior to randomisation. Treatment with an approved 1st or 2nd generation EGFR-TKI during screening is allowed as long as the washout period of 8 days or 5 half-lives is guaranteed. 4. Previous chemotherapy and experimental anticancer therapy within 4 weeks, anticancer immunotherapy within 2 weeks, or anticancer hormonal treatment within 2 weeks, of the first administration of study drug. 5. Radiotherapy within 4 weeks prior to randomisation except as follows: a. Palliative radiotherapy to regions other than the chest is allowed up to 2 weeks prior to randomization; b. Single dose palliative radiotherapy for symptomatic metastasis within 2 weeks prior to randomisation may be allowed but must be discussed with the sponsor. 6. Major surgery within 4 weeks prior to randomisation or scheduled during the projected course of the study. 7. Known history of hypersensitivity to BI 1482694 or any of its excipients or drugs with a chemical structure similar to BI 1482694. 8. Known history of hypersensitivity to cisplatin, carboplatin or pemetrexed or any of their excipients. 9. History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of ? 3, unstable angina or poorly controlled arrhythmia which are considered as clinically relevant by the investigator. Myocardial infarction within 6 months prior to randomisation. 10. Female patients of childbearing potential (see Section 4.2.2.3) who are nursing or pregnant or do not agree to submit to pregnancy testing required by this protocol. 11. Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient?s ability to comply with the trial or interfere with the evaluation of the efficacy and safety of the test drug. 12. Previous or concomitant malignancies at other sites, except: a. effectively treated non-melanoma skin cancers; b. effectively treated carcinoma in situ of the cervix; c. effectively treated ductal carcinoma in situ; d. other effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured. 13. Known pre-existing interstitial lung disease. 14. Any history or presence of uncontrolled gastrointestinal disorders that could affect the intake and/or absorption of the study drug (e.g. nausea, vomiting, Crohn?s disease, ulcerative colitis, chronic diarrhoea, malabsorption) in the opinion of the investigator. 15. Known active hepatitis B infection (defined as presence of HepB sAg and/or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier. 16. Left ventricular ejection fraction (LVEF) < 50%. 17. Leptomeningeal carcinomatosis. 18. Presence or history of uncontrolled or symptomatic brain or subdural metastases, unless considered stable by the investigator and local therapy was completed. Use of corticosteroids is al
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy and safety of BI 1482694 versus standard platinum doublet chemotherapy as a second line treatment for patients with locally advanced or metastatic NSCLC whose disease progressed on or after one prior 1st line EGFR-TKI therapy and whose tumours carry at least one EGFR activating mutation and a T790M mutation versus standard platinum doublet chemotherapy.;Secondary Objective: ---;Primary end point(s): Primary endpoint: - Progression free survival (PFS) according to RECIST 1.1 by independent review.;Timepoint(s) of evaluation of this end point: Every 6 weeks up until Week 60 and every 12 weeks thereafter until PD or start of subsequent anti-cancer therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall Survival (OS) - Objective response (OR) according to RECIST 1.1 by independent review - Time to and duration of OR according to RECIST 1.1 by independent review - Disease Control (DC) and tumour shrinkage (according to RECIST 1.1 by independent review) - Time to deterioration in Patient Reported Outcomes (PROs) of: cough (EORTC QLQ-LC13: Q1); dyspnoea (EORTC QLQ-LC13: Q3-5 and EORTC QLQC30:Q8); chest pain (EORTC QLQ-LC13: Q10); NSCLC specific symptoms of NSCLC SAQ (R99-1213, R07-2064; R12-5607; R07-2060). - Deterioration of NSCLC specific symptoms (NSCLC-SAQ).;Timepoint(s) of evaluation of this end point: OS ? every 3 weeks until PD/start of subsequent anti-cancer therapy and then every 60 days until death. OR ? imaging visits, - all RECIST endpoints as imaging visits frequency; QoL questionnaires ? every 3 weeks until death or PD/start of subsequent anti-cancer therapy. | — |
Countries
Australia, Austria, Belgium, Canada, China, France, Germany, Hong Kong, India, Italy, Korea, Republic of, Malaysia, Philippines, Poland, Portugal, Russian Federation, Serbia, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States, Vietnam
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co KG
Outcome results
None listed