Xentuzumab (BI 836845) Plus Afatinib in Patients With Epidermal Growth Factor Receptor (EGFR) Mutant Non-small Cell Lung Cancer (NSCLC)

Phase 1

Completed

Conditions: Carcinoma, Non-Small-Cell Lung

Interventions: Drug: Xentuzumab
Drug: Afatinib

Registration Number: NCT02191891

Lead Sponsor: Boehringer Ingelheim

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Xentuzumab + Afatinib 30 milligram (mg) - Part A	Xentuzumab	Patients received intravenous infusion of Xentuzumab 1000 milligram (mg) delivered over 60 minutes per week for 4 weeks, in combination with once daily oral treatment of Afatinib 30 mg film-coated tablet. Dose confirmation part (Part A).
Xentuzumab + Afatinib 30 milligram (mg) - Part A	Afatinib	Patients received intravenous infusion of Xentuzumab 1000 milligram (mg) delivered over 60 minutes per week for 4 weeks, in combination with once daily oral treatment of Afatinib 30 mg film-coated tablet. Dose confirmation part (Part A).
Xentuzumab + Afatinib 40 mg - Part A	Xentuzumab	Patients received intravenous infusion of Xentuzumab 1000 milligram (mg) delivered over 60 minutes per week for 4 weeks, in combination with once daily oral treatment of Afatinib 40 mg film-coated tablet. Dose confirmation part (Part A).
Xentuzumab + Afatinib 40 mg - Part A	Afatinib	Patients received intravenous infusion of Xentuzumab 1000 milligram (mg) delivered over 60 minutes per week for 4 weeks, in combination with once daily oral treatment of Afatinib 40 mg film-coated tablet. Dose confirmation part (Part A).
Xentuzumab + Afatinib 20 mg - Part B	Xentuzumab	Patients received intravenous infusion of Xentuzumab 1000 milligram (mg) delivered over 60 minutes per week for 4 weeks, in combination with once daily oral treatment of Afatinib 20 mg film-coated tablet. Expansion part (Part B).
Xentuzumab + Afatinib 20 mg - Part B	Afatinib	Patients received intravenous infusion of Xentuzumab 1000 milligram (mg) delivered over 60 minutes per week for 4 weeks, in combination with once daily oral treatment of Afatinib 20 mg film-coated tablet. Expansion part (Part B).
Xentuzumab + Afatinib 30 mg - Part B	Xentuzumab	Patients received intravenous infusion of Xentuzumab 1000 milligram (mg) delivered over 60 minutes per week for 4 weeks, in combination with once daily oral treatment of Afatinib 30 mg film-coated tablet. Expansion part (Part B).
Xentuzumab + Afatinib 30 mg - Part B	Afatinib	Patients received intravenous infusion of Xentuzumab 1000 milligram (mg) delivered over 60 minutes per week for 4 weeks, in combination with once daily oral treatment of Afatinib 30 mg film-coated tablet. Expansion part (Part B).
Xentuzumab + Afatinib 40 mg - Part B	Xentuzumab	Patients received intravenous infusion of Xentuzumab 1000 milligram (mg) delivered over 60 minutes per week for 4 weeks, in combination with once daily oral treatment of Afatinib 40 mg film-coated tablet. Expansion part (Part B).
Xentuzumab + Afatinib 40 mg - Part B	Afatinib	Patients received intravenous infusion of Xentuzumab 1000 milligram (mg) delivered over 60 minutes per week for 4 weeks, in combination with once daily oral treatment of Afatinib 40 mg film-coated tablet. Expansion part (Part B).

Primary Outcome Measures

Name	Time	Method
Number of Patients With Dose Limiting Toxicities (DLT) - Part A	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	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	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Disease Control (DC) - Part B	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.	DC was defined as best overall response of complete response (CR) or partial response (PR) or stable disease (SD) according to 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.
Time to OR - Part B	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.	Time to OR, defined as the time from first treatment administration until first documented CR or PR. For patients with OR, time to OR was summarised on a patient level.
Duration of OR - Part B	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.	Duration of OR, defined as the time from first documented CR or PR until the earliest of disease progression or death among patients with OR - Part B. For patients with OR, duration of OR was summarised on a patient level.

Trial Locations

Locations (10): Severance Hospital
🇰🇷
Seoul, Korea, Republic of
National Cancer Centre Singapore
🇸🇬
Singapore, Singapore
National Hospital Organization Kyushu Cancer Center
🇯🇵
Fukuoka, Fukuoka, Japan
Chungbuk National University Hospital
🇰🇷
Cheongju, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Chang Gung Memorial Hospital Chiayi
🇨🇳
Chiayi, Taiwan
Kaohsiung Chang Gung Memorial Hospital
🇨🇳
Kaohsiung, Taiwan
NCKUH
🇨🇳
Tainan, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Severance Hospital
🇰🇷Seoul, Korea, Republic of