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

Carcinoma, Non-Small-Cell Lung Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02191891
• Other study ID #: 1280.16
• Status: Completed
• Phase: Phase 1
• Start date: October 21, 2014
• Est. completion date: April 18, 2018

Study information

• Verified date: April 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: April 18, 2018
• Est. primary completion date: April 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• BI 836845
Human monoclonal antibody. Two dose levels (high or low) depending on the dose cohort explored
• 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

Locations

Country	Name	City	State
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka, Fukuoka
Korea, Republic of	Chungbuk National University Hospital	Cheongju
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Singapore	National Cancer Centre	Singapore
Taiwan	Chang Gung Memorial Hospital Chiayi	Chiayi
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	NCKUH	Tainan
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Japan,  Korea, Republic of,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) of BI 836845 in combination with afatinib - part A		up to 12 months
Primary	Dose limiting toxicity (DLT) during the first treatment course - part A		up to 28 days
Primary	Objective response (OR), defined as complete response (CR) or partial response (PR)		up to 12 months
Secondary	Disease control (DC), defined as complete response (CR), partial response (PR) or stable disease (SD)		up to 12 months
Secondary	Time to objective response, defined as the duration of time from the date of first treatment administration until objective response		up to 12 months
Secondary	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