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Carcinoma, Non-Small-Cell LungPhase 1NCT02191891

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

A Phase 1 study testing Xentuzumab and Afatinib in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 10 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
Xentuzumab and Afatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
10 sitesin 4 countries
Study dates
21 Oct 2014to 18 Apr 2018
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

10 sites in 4 countries.

10 sites in 4 countries

South Korea4 sites

  • Chungbuk National University Hospital

    Cheongju-si, 361-771

  • Severance Hospital

    Seoul, 03722

  • Samsung Medical Center

    Seoul, 135-710

  • Asan Medical Center

    Seoul, 138-736

Other trials in South Korea

Taiwan4 sites

  • Chang Gung Memorial Hospital Chiayi

    Chiayi City, 613

  • Kaohsiung Chang Gung Memorial Hospital

    Kaohsiung City, 83301

  • NCKUH

    Tainan, 704

  • National Taiwan University Hospital

    Taipei, 100

Other trials in Taiwan

Japan1 site

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka, Fukuoka, 811-1395

Other trials in Japan

Singapore1 site

  • National Cancer Centre Singapore

    Singapore, 169610

Other trials in Singapore

About this study

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

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

Being tested
Xentuzumab, Afatinib
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • XentuzumabDrug

    Also called BI 836845

    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.

  • AfatinibDrug

    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.

Study groups in NCT02191891
Study groupRoleWhat they receive
Xentuzumab + Afatinib 30 milligram (mg) - Part AExperimentalPatients 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).
Receives: Drug: Xentuzumab; Drug: Afatinib
Xentuzumab + Afatinib 40 mg - Part AExperimentalPatients 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).
Receives: Drug: Xentuzumab; Drug: Afatinib
Xentuzumab + Afatinib 20 mg - Part BExperimentalPatients 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).
Receives: Drug: Xentuzumab; Drug: Afatinib
Xentuzumab + Afatinib 30 mg - Part BExperimentalPatients 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).
Receives: Drug: Xentuzumab; Drug: Afatinib
Xentuzumab + Afatinib 40 mg - Part BExperimentalPatients 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).
Receives: Drug: Xentuzumab; Drug: Afatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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.

    Measured: 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)

  1. Number of Participants With Disease Control (DC) - Part B

    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.

    Measured: 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.

  2. Time to OR - Part B

    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.

    Measured: 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.

  3. Duration of OR - Part B

    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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2014 (estimated)
  2. Study start21 Oct 2014
  3. Primary completion18 Apr 2018
  4. Study completion18 Apr 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02191891
Sponsor's protocol ID
1280.16
Status last verified
Jun 2025
First submitted
14 Jul 2014
Last updated
25 Jun 2025
Individual data sharing
Yes: Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Xentuzumab and Afatinib in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 10 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in South Korea, Taiwan, Japan, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Dose Limiting Toxicities (DLT) - Part A (time frame: During the first treatment course, up to 28 days.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02191891.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2025.

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