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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02191891
Recruitment Status : Completed
First Posted : July 16, 2014
Last Update Posted : May 1, 2018
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: BI 836845 Drug: afatinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 21, 2014
Actual Primary Completion Date : April 18, 2018
Actual Study Completion Date : April 18, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BI 836845 + afatinib
BI 836845 low or high dose (weekly IV infusion), afatinib 30mg or 40mg (once daily oral dosing)
Drug: BI 836845
Human monoclonal antibody. Two dose levels (high or low) depending on the dose cohort explored
Other Name: Xentuzumab

Drug: afatinib
Irreversible EGFR tyrosine kinase inhibitor. Two dose levels (30 mg, 40 mg) depending on the dose cohort explored or determined dose at part A

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of BI 836845 in combination with afatinib - part A [ Time Frame: up to 12 months ]
  2. Dose limiting toxicity (DLT) during the first treatment course - part A [ Time Frame: up to 28 days ]
  3. Objective response (OR), defined as complete response (CR) or partial response (PR) [ Time Frame: up to 12 months ]

Secondary Outcome Measures :
  1. Disease control (DC), defined as complete response (CR), partial response (PR) or stable disease (SD) [ Time Frame: up to 12 months ]
  2. Time to objective response, defined as the duration of time from the date of first treatment administration until objective response [ Time Frame: up to 12 months ]
  3. Duration of objective response, defined as the duration of time from first objective response to the date of first objective tumour progression or death due to any cause [ Time Frame: up to 12 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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. 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

Exclusion criteria:

  • 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 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02191891

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National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka, Japan, 811-1395
Korea, Republic of
Chungbuk National University Hospital
Cheongju, Korea, Republic of, 361-771
Severance Hospital, Yonsei University Health System
Seoul, Korea, Republic of, 120-752
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Asan Medical Center
Seoul, Korea, Republic of, 138-736
National Cancer Centre
Singapore, Singapore, 169610
Chang Gung Memorial Hospital Chiayi
Chiayi, Taiwan, 613
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung, Taiwan, 83301
Tainan, Taiwan, 704
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
Boehringer Ingelheim
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim
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Responsible Party: Boehringer Ingelheim Identifier: NCT02191891    
Other Study ID Numbers: 1280.16
First Posted: July 16, 2014    Key Record Dates
Last Update Posted: May 1, 2018
Last Verified: April 2018
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action