Part A: To determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of Xentuzumab (BI 836845) in combination with afatinib in patients with non-small cell lung cancer with progression following prior treatment (EGFR TKI or platinum-based chemotherapy). Part B: To evaluate the early anti-tumour activity of Xentuzumab (BI 836845) in combination with afatinib in patients with EGFR mutant non-small cell lung cancer with progression following prior irreversible EGFR TKIs. Part A and B: To evaluate the safety and pharmacokinetics of BI 836845 in combination with afatinib in patients with non-small cell lung cancer
Name: BI 836845
Description: Human monoclonal antibody. Two dose levels (high or low) depending on the dose cohort exploredType: DrugBI 836845 + afatinib
Name: afatinib
Description: Irreversible EGFR tyrosine kinase inhibitor. Two dose levels (30 mg, 40 mg) depending on the dose cohort explored or determined dose at part AType: DrugBI 836845 + afatinib
Single Group Assignment
There are 2 SNPs
Inclusion criteria: - Aged 18 years or older - Pathologically confirmed of advanced and/or metastatic stage IIIb/IV non-small cell carcinoma of lung - Activating EGFR mutation (exon 19 deletion, L858R, G719X, L861X) - Presence of EGFR activating mutation and absence of EGFR T790M in the tumour associated with the latest disease progression. --- L858R ---
AZD9291 or CO-1686) Inclusion criteria: - Aged 18 years or older - Pathologically confirmed of advanced and/or metastatic stage IIIb/IV non-small cell carcinoma of lung - Activating EGFR mutation (exon 19 deletion, L858R, G719X, L861X) - Presence of EGFR activating mutation and absence of EGFR T790M in the tumour associated with the latest disease progression. --- L858R ---
Inclusion criteria: - Aged 18 years or older - Pathologically confirmed of advanced and/or metastatic stage IIIb/IV non-small cell carcinoma of lung - Activating EGFR mutation (exon 19 deletion, L858R, G719X, L861X) - Presence of EGFR activating mutation and absence of EGFR T790M in the tumour associated with the latest disease progression. --- L858R --- --- T790M ---
AZD9291 or CO-1686) Inclusion criteria: - Aged 18 years or older - Pathologically confirmed of advanced and/or metastatic stage IIIb/IV non-small cell carcinoma of lung - Activating EGFR mutation (exon 19 deletion, L858R, G719X, L861X) - Presence of EGFR activating mutation and absence of EGFR T790M in the tumour associated with the latest disease progression. --- L858R --- --- T790M ---