Clinical Trials /

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

NCT02191891

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 1280.16
  • NCT ID: NCT02191891

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
BI 836845XentuzumabBI 836845 + afatinib
afatinibBI 836845 + afatinib

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
BI 836845 + afatinibExperimentalBI 836845 low or high dose (weekly IV infusion), afatinib 30mg or 40mg (once daily oral dosing)
  • BI 836845
  • afatinib

Eligibility Criteria

        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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of BI 836845 in combination with afatinib - part A
Time Frame:up to 12 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease control (DC), defined as complete response (CR), partial response (PR) or stable disease (SD)
Time Frame:up to 12 months
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Boehringer Ingelheim

Last Updated

September 5, 2017