A Phase Ib Open-label Clinical Trial of Once Daily Oral Treatment of Afatinib Plus Weekly Intravenous Infusion of Xentuzumab (BI 836845) in Patients With EGFR Mutant Non-small Cell Lung Cancer With Progression Following Prior EGFR Tyrosine Kinase Inhibitors

Number of Patients With Dose Limiting Toxicities (DLT) - Part A

时间窗: During the first treatment course, up to 28 days.

DLT Criteria: Common Terminology Criteria for Adverse Events(CTCAE) CTCAE Grade (G) 4 neutropenia lasting ≥7 days; Febrile neutropenia with a single/sustained temperature of ≥38.3°C for \>1 hour; Documented infection with absolute neutrophil count (ANC) \<1.0 x 109/L; G 3/4 thrombocytopenia associated with bleeding requiring platelet transfusion; G 2/higher decrease in cardiac left ventricular function; G 2 diarrhea lasting for ≥7 days; G ≥3 diarrhea; G≥3 nausea/vomiting; G≥3 skin rash; aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \>5 x Upper limit of normal (ULN)/\>baseline value +4 x ULN; G≥3 fatigue/asthenia lasting for \>7 days; G≥3 hyperglycemia lasting \>48 hours; All other non-hematologic adverse events(AEs) of G≥3 (except alopecia, infusion reaction, and allergic reaction) that led to an interruption of afatinib/xentuzumab for \>14 days until recovery to baseline/G 1; Any other study drug-related toxicity considered significant enough to qualify as DLT.

Maximum Tolerated Dose (MTD) - Part A

时间窗: During the first treatment course, up to 28 days.

Maximum tolerated dose (MTD) of Xentuzumab in combination with Afatinib, in patients with non-small cell lung cancer with progression following prior treatment, based on the occurrence of dose limiting toxicity (DLT) during the first treatment course. MTD was defined as the highest dose level examined of trial medication, at which no more than 1 out of 6 patients experienced a DLT during the MTD evaluation period.

Number of Participants With Objective Response (OR) - Part B

时间窗: Tumour assessment was performed every 4 weeks after the start of treatment for first 8 weeks, in 8-week intervals thereafter and in 12-week interval after Course 16 until disease progression or the start of further anti-cancer treatment, up to 1200 days.

OR was defined as best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, where best overall response was defined according to RECIST v1.1 from first administration of trial medication until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy.