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

NCT02191891 | Completed Phase 1 Results

• 1 other identifier: 1280.16
• Study Type: interventional
• Target: 32
• Locations: 4 countries
• Sites: 10

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

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (3)

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

  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.

  During the first treatment course, up to 28 days.

• Maximum Tolerated Dose (MTD) - Part A

  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.

  During the first treatment course, up to 28 days.

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

  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.

  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.

Secondary Outcomes (3)

• 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.

• 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.

• 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.

Study Arms (5)

Xentuzumab + Afatinib 30 milligram (mg) - Part A

EXPERIMENTAL

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).

Drug: Xentuzumab; Drug: Afatinib

Xentuzumab + Afatinib 40 mg - Part A

EXPERIMENTAL

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).

Drug: Xentuzumab; Drug: Afatinib

Xentuzumab + Afatinib 20 mg - Part B

EXPERIMENTAL

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).

Drug: Xentuzumab; Drug: Afatinib

Xentuzumab + Afatinib 30 mg - Part B

EXPERIMENTAL

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).

Drug: Xentuzumab; Drug: Afatinib

Xentuzumab + Afatinib 40 mg - Part B

EXPERIMENTAL

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).

Drug: Xentuzumab; Drug: Afatinib

Interventions

Xentuzumab DRUG

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 film-coated tablet.

Also known as: BI 836845

Xentuzumab + Afatinib 20 mg - Part B; Xentuzumab + Afatinib 30 mg - Part B; Xentuzumab + Afatinib 30 milligram (mg) - Part A; Xentuzumab + Afatinib 40 mg - Part A; Xentuzumab + Afatinib 40 mg - Part B

Afatinib DRUG

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 film-coated tablet.

Xentuzumab + Afatinib 20 mg - Part B; Xentuzumab + Afatinib 30 mg - Part B; Xentuzumab + Afatinib 30 milligram (mg) - Part A; Xentuzumab + Afatinib 40 mg - Part A; Xentuzumab + Afatinib 40 mg - Part B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. 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
• Life expectancy of \>= 3 months
• Fasting plasma glucose \< 8.9 mmol/L (\< 160mg/dL) and HbA1C \< 8%
• Adequate organ function
• 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 qualify 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (10)

National Hospital Organization Kyushu Cancer Center

Fukuoka, Fukuoka, 811-1395, Japan

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Chungbuk National University Hospital

Cheongju-si, 361-771, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Chang Gung Memorial Hospital Chiayi

Chiayi City, 613, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

Location

NCKUH

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Links

• Related Info

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

xentuzumab; Afatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2014
• First Posted: July 16, 2014
• Study Start: October 21, 2014
• Primary Completion: April 18, 2018
• Study Completion: April 18, 2018
• Last Updated: June 25, 2025
• Results First Posted: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Locations

KR (4); SG (1); JP (1); TW (4)