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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02191891
• Date of registration: 14/07/2014
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim
• Public title: Xentuzumab (BI 836845) Plus Afatinib in Patients With Epidermal Growth Factor Receptor (EGFR) Mutant Non-small Cell Lung Cancer (NSCLC)
• Scientific 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
• Date of first enrolment: October 21, 2014
• Target sample size: 32
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02191891
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Japan, Korea, Republic of, Singapore, Taiwan

Contacts

• Name: Boehringer Ingelheim
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion 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)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Carcinoma, Non-Small-Cell Lung

Intervention(s)

Drug: BI 836845

Drug: afatinib

Primary Outcome(s)

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

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

Objective response (OR), defined as complete response (CR) or partial response (PR) [Time Frame: up to 12 months]

Secondary Outcome(s)

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]

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]

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

Secondary ID(s)

1280.16

Source(s) of Monetary Support

Please refer to primary and secondary sponsors