Presence of EGFR activating mutation and absence of EGFR T790M in the tumour associated with the latest disease progression. Only applicable in Part B
Must have adequate fresh or archival tumour tissue at the late disease progression immediately prior to the study entry
Part A: Progression of disease (RECIST 1.1) while on continuous treatment with single EGFR TKI or for histology other than adenocarcinoma and without prior EGFR TKI treatment: progression of disease (RECIST v1.1) on platinum-based chemotherapy. Part B: Progression of disease (RECIST v1.1) while on continuous treatment with single agent of the second generation irreversible EGFR TKI (e.g. afatinib or dacomitinib)
No intervening systemic therapy between cessation of EGFR TKI and study treatment
Patient must have measurable disease per RECIST 1.1 presented after tumour biopsy for the late disease progression
Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1
Recovered from any previous therapy related toxicity to \<= Grade 1 at study entry (except for stable sensory neuropathy \<= Grade 2 and alopecia)
Written informed consent that is consistent with ICH-GCP guidelines and local regulations
No known potentially targetable mutation other than IGF signaling pathway or EGFR or no available treatment for potentially targetable mutation
You may not be if
Part A only: For patient who has been treated with afatinib: last treatment at reduced dose below the assigned dose level
Patient whose disease progressed on insufficient dose of EGFR TKI immediately prior to study in the opinion of the investigator
More than 2 prior EGFR TKI treatment regimens for Part B
Chemotherapy, biological therapy or investigational agents (except EGFR TKIs) within 4 weeks
Use of previous EGFR TKIs except afatinib within 3 days
Radiotherapy within 4 weeks prior to the start of study treatment
Active brain or subdural metastases
Meningeal carcinomatosis.
Major surgery (as judged by the investigator) within 4 weeks
Known hypersensitivity to afatinib, monoclonal antibody
Prior severe infusion-related reaction to a monoclonal antibody
History or presence of clinically relevant cardiovascular abnormalities
Female patients of childbearing potential (see Section 4.2.2.3) and male who are able to father a child
Any history of or concomitant condition that, in the opinion of the investigator not to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug
Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured.
Disease that is considered by the investigator to be rapidly progressing or life threatening such as extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumour (subjects who are intended for urgent chemotherapy)
Requiring treatment with any of the prohibited concomitant medications
Known pre-existing interstitial lung disease (ILD)
Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug
Active hepatitis B infection active hepatitis C infection and/or known HIV carrier.
Previous treatment with agents targeting the insulin like growth factor (IGF) signalling pathway.
Previous treatment with EGFR TKI which cannot be documented as either reversible or irreversible (Part B only)
Part B only: Prior treatment with third generation irreversible EGFR TKI (e.g. AZD9291 or CO-1686)
Clareo Health | Xentuzumab (BI 836845) Plus Afatinib in Patients With Epidermal Growth Factor Receptor (EGFR) Mutant Non-small Cell Lung Cancer (NSCLC)
