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

Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT02191891
Collaborator
(none)
32
Enrollment
10
Locations
1
Arm
41.9
Actual Duration (Months)
3.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
Phase 1

Study Design

Study Type:
Interventional
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 :
Oct 21, 2014
Actual Primary Completion Date :
Apr 18, 2018
Actual Study Completion Date :
Apr 18, 2018

Arms and Interventions

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 Names:
  • 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

    Outcome Measures

    Primary Outcome Measures

    1. Maximum tolerated dose (MTD) of BI 836845 in combination with afatinib - part A [up to 12 months]

    2. Dose limiting toxicity (DLT) during the first treatment course - part A [up to 28 days]

    3. Objective response (OR), defined as complete response (CR) or partial response (PR) [up to 12 months]

    Secondary Outcome Measures

    1. Disease control (DC), defined as complete response (CR), partial response (PR) or stable disease (SD) [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 [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 [up to 12 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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 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.

    • 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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Hospital Organization Kyushu Cancer Center Fukuoka, Fukuoka Japan 811-1395
    2 Chungbuk National University Hospital Cheongju Korea, Republic of 361-771
    3 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 120-752
    4 Samsung Medical Center Seoul Korea, Republic of 135-710
    5 Asan Medical Center Seoul Korea, Republic of 138-736
    6 National Cancer Centre Singapore Singapore 169610
    7 Chang Gung Memorial Hospital Chiayi Chiayi Taiwan 613
    8 Kaohsiung Chang Gung Memorial Hospital Kaohsiung Taiwan 83301
    9 NCKUH Tainan Taiwan 704
    10 National Taiwan University Hospital Taipei Taiwan 100

    Sponsors and Collaborators

    • Boehringer Ingelheim

    Investigators

    • Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Boehringer Ingelheim
    ClinicalTrials.gov Identifier:
    NCT02191891
    Other Study ID Numbers:
    • 1280.16
    First Posted:
    Jul 16, 2014
    Last Update Posted:
    May 1, 2018
    Last Verified:
    Apr 1, 2018
    Additional relevant MeSH terms:
    Carcinoma, Non-Small-Cell Lung
    Afatinib

    Study Results

    No Results Posted as of May 1, 2018