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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03468426




Registration number
NCT03468426
Ethics application status
Date submitted
8/03/2018
Date registered
16/03/2018
Date last updated
1/12/2020

Titles & IDs
Public title
A Study to Test Different Doses of BI 836880 Combined With BI 754091 in Patients With Advanced Non-small Cell Lung Cancer Followed by Other Types of Advanced Solid Tumours
Scientific title
An Open Label Phase Ib Dose Finding Study of BI 836880 in Combination With BI 754091 to Characterize Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy in Patients With Locally Advanced or Metastatic Non-squamous Non-Small Cell Lung Cancer and in Other Solid Tumors
Secondary ID [1] 0 0
2017-001378-41
Secondary ID [2] 0 0
1336-0011
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-squamous, Non-Small-Cell Lung Cancer 0 0
Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BI 836880
Treatment: Drugs - BI 754091

Experimental: BI 836880 + BI 754091 -


Treatment: Drugs: BI 836880
intra-venous infusion

Treatment: Drugs: BI 754091
intra-venous infusion

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
PART 1: Number of patients with Dose Limiting Toxicities (DLTs) within the first cycle of treatment
Timepoint [1] 0 0
Up to 3 weeks
Primary outcome [2] 0 0
PART 2: Shrinkage estimator of objective response
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [1] 0 0
PART 1:Adverse events (AEs), drug related AEs, drug related AEs leading to dose reduction or discontinuation during treatment period
Timepoint [1] 0 0
Up to 3 weeks
Secondary outcome [2] 0 0
PART 1: AUC 0-504h (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours after the first and fourth infusion cycle)
Timepoint [2] 0 0
Up to 504 hours after first and fourth infusion cycle
Secondary outcome [3] 0 0
PART 2:Adverse events (AEs), drug related AEs, drug related AEs leading to dose reduction or discontinuation during treatment period
Timepoint [3] 0 0
Up to 3 weeks
Secondary outcome [4] 0 0
PART 2: Disease control (DC)
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
PART 2: Duration of objective response (DoR)
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
PART 2: Progression-free survival (PFS)
Timepoint [6] 0 0
Up to 3 years
Secondary outcome [7] 0 0
PART 2: Tumour shrinkage (in millimeters)
Timepoint [7] 0 0
Up to 3 years
Secondary outcome [8] 0 0
PART 2: AUC 0-504h (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours after the first and fourth infusion cycle)
Timepoint [8] 0 0
Up to 504 hours after first and fourth infusion cycle
Secondary outcome [9] 0 0
PART 1: Cmax (maximum measured concentration of the analyte in plasma)
Timepoint [9] 0 0
Up to 12 weeks
Secondary outcome [10] 0 0
PART 1: tmax (time from dosing to maximum measured concentration of the analyte in plasma)
Timepoint [10] 0 0
Up to 12 weeks
Secondary outcome [11] 0 0
PART 2: Cmax (maximum measured concentration of the analyte in plasma)
Timepoint [11] 0 0
Up to 12 weeks
Secondary outcome [12] 0 0
PART 2: tmax (time from dosing to maximum measured concentration of the analyte in plasma)
Timepoint [12] 0 0
Up to 12 weeks

Eligibility
Key inclusion criteria
Part 1:

- Of full age (according to local legislation, usually = 18 years) at screening.

- Pathologically confirmed locally advanced or metastatic non-squamous NSCLC with PDL-1
expression available and >1% by IHC (as defined by the Pembrolizumab companion
diagnostic test, determined by appropriate local pathology lab.

- No previous treatment with check-point inhibitor. Or patients with checkpoint
inhibitor based treatment as last therapy before entering the trial.

- Documented disease progression or relapse (based on investigator's assessment) during
or after completion of at least 2 cycles of platinum-based chemotherapy as first line
treatment of Stage IIIB/IV non- squamous NSCLC or for checkpoint inhibitor experienced
patients during or after completion of at least 2 cycles of platinum-based
chemotherapy and a checkpoint inhibitor treatment (monotherapy or in combination with
chemotherapy). This includes patients relapsing within 6 months of completing
(neo)adjuvant/curative-intent chemotherapy/CPI or chemoradiotherapy

- At least one target lesion (outside the brain) that can be accurately measured per
Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.

- Lesion with a diameter = 2cm assessed by radiologist as suitable for DCE-MRI
evaluation (Mandatory in Part 1, optional in Part 2)

- Eastern Cooperative Oncology Group (ECOG) performance status = 1 Life expectancy = 3
months after start of the treatment in the opinion of the investigator

- Recovery from all reversible adverse events of previous anti-cancer therapies to
baseline or CTCAE grade 1, except for alopecia (any grade), sensory peripheral
neuropathy , must be = CTCAE grade 2 or considered not clinically significant.

- Signed and dated written informed consent in accordance with ICH-GCP and local
legislation prior to admission to the trial

- Availability and willingness to provide a fresh tumour tissue sample obtained at
baseline, and after 2 cycles of treatment

- Adequate organ function defined as all of the following (all screening labs should be
performed at local lab within 10 days prior to treatment initiation)

- Male or female patients. Women of childbearing potential (WOCBP)1 and men able to
father a child must be ready and able to use highly effective methods of birth control
per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used
consistently and correctly, starting with the screening visit and through 6 months
after the last dose of BI 836880 and BI 754091 treatment, respectively. A list of
contraception methods meeting these criteria is provided in the patient information
Note: Female patients of childbearing potential must have a negative serum pregnancy
test within 72 hours prior to taking study medication during the screening period. At
the following visits according to the flowchart a urine and/or serum pregnancy test is
required. If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required. The serum pregnancy test must be negative for the
patient to be eligible.

Part 1 & Part 2:

- Of full age (according to local legislation, usually = 18 years) at screening

- At least one measurable target lesion outside the brain (excluding the glioblastoma
patients), that can be accurately measured per RECIST 1.1

- ECOG performance status = 1 (For glioblastoma cohort Karnofsky status is applicable;
see below)

- Adequate organ function as all of the following (all screening labs should be
performed at local lab within approximately 72 hours prior to treatment initiation)

- Availability and willingness to provide a fresh tumor tissue sample obtained after
relapse or progression on or after prior therapy. For Part 2, In case a fresh biopsy
cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived
specimen obtained up to 6 months prior to cycle 1, visit 1 (C1V1) may be submitted in
case no systemic antineoplastic therapy has been administered between the biopsy and
C1V1 (except for cohort D). For cohorts E, F and G, a fresh on-treatment biopsy is
mandatory at C3D1, if possible from the same lesion as the pre-treatment biopsy.

- Life expectancy = 3 months after start of the treatment in the opinion of the
investigator

- Recovery from all reversible adverse events of previous anti-cancer therapies to
baseline or CTCAE grade 1, except for alopecia (any grade), sensory peripheral
neuropathy , must be = CTCAE grade 2 or considered not clinically significant.

- Signed and dated written informed consent in accordance with ICH-GCP and local
legislation prior to admission to the trial

- Male or female patients. Women of childbearing potential (WOCBP)2 and men able to
father a child must be ready and able to use highly effective methods of birth control
per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used
consistently and correctly, for the entire duration of the trial treatment intake and
for 6 months after the end of the trial treatment. A list of contraception methods
meeting these criteria is provided in the patient information.

Note: Female patients of childbearing potential must have a negative serum pregnancy test
within 72 hours during the screening period. At the following visits according to the
flowchart, a urine and/or serum pregnancy test is required. If the urine test is positive
or cannot be confirmed as negative, a serum pregnancy test will be required. The serum
pregnancy test must be negative for the patient to be eligible.- Further inclusion criteria
apply
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

Part 1:

- Known hypersensitivity to the trial drugs or their excipients or risk of allergic of
anaphylactic reaction to drug product according to Investigator judgement (e.g.
patient with history of anaphylactic reaction or autoimmune disease that is not
controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids,
or the equivalent of </= 10 mg/day prednisone).

- Known immunodeficiency virus infection or an active hepatitis B or C virus infection.

- History of severe hypersensitivity reactions to other mAbs.

- Immunosuppressive corticosteroid doses (> 10 mg prednisone daily or equivalent) within
4 weeks prior to the first dose of trial medication.

- Current or prior treatment with any systemic anti-cancer therapy either within 28 days
or a minimum of 5 half-lives, whichever is shorter before start of treatment.

- Serious concomitant disease, especially those affecting compliance with trial
requirements or which are considered relevant for the evaluation of the endpoints of
the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers
(gastrointestinal tract, skin) or laboratory abnormality that may increase the risk
associated with trial participation or trial drug administration, and in the judgment
of the investigator would make the patient inappropriate for entry into the trial.

- Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment,
or planned surgical procedures during the trial period.

- Patients with personal or family history of QT prolongation and/or long QT syndrome,
or prolonged QTcF at baseline (> 480 ms).

- Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension,
unstable angina, history of infarction within past 6 months, congestive heart failure
> NYHA II).

Uncontrolled hypertension defined as: Blood pressure in rested and relaxed condition >= 140
mmHg, systolic or >= 90 mmHg diastolic (with or without medication), measured according to
Appendix 10.2.

- LVEF < 50%

- History of severe hemorrhagic or thromboembolic event in the past 12 months (excluding
central venous catheter thrombosis and peripheral deep vein thrombosis).

- Known inherited predisposition to bleeding or to thrombosis in the opinion of the
investigator.

- Patient with brain metastases that are symptomatic and/or require therapy.

- Patients who require full-dose anticoagulation (according to local guidelines). No
Vitamin K antagonist and other anticoagulation allowed; LMWH allowed only for
prevention not for curative treatment.

- History of pneumonitis within the last 5 years

- Patients who are under judicial protection and patients who are legally
institutionalized.

- Patients unable or unwilling to comply with protocol

- Previous enrolment in this trial (Part 1 or Part 2).

- Chronic alcohol or drug abuse or any condition that, in the investigator's opinion,
makes them an unreliable trial patient or unlikely to complete the trial.

- Women who are pregnant, nursing, or who plan to become pregnant in the trial

Part 2:

- Known hypersensitivity to the trial drugs or their excipients or risk of allergic of
anaphylactic reaction to drug product according to Investigator judgement (e.g.
patient with history of anaphylactic reaction or autoimmune disease that is not
controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids,
or the equivalent of </= 10 mg/day prednisone).

- Not more than one CPI based treatment regimen prior to entering study (eg.
anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1),
anti-PD-L2, or anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4)
antibody) unless combination CPIs approved by the local regulatory agencies; For eg.,
Melanoma cohort (Cohort E).

- Known HIV infection

- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (exception for
patients in HCC cohorts; Cohorts F& G).

- History of severe hypersensitivity reactions to other mAbs.

- Immunosuppressive corticosteroid doses (> 10 mg prednisone daily or equivalent) within
4 weeks prior to the first dose of trial medication except for control of cerebral
edema in case of recurrent glioblastoma (cohort D).

- Current or prior treatment with any systemic anti-cancer therapy (including
radiotherapy) either within 28 days or a minimum of 5 half-lives, whichever is shorter
before start of treatment

- Serious concomitant disease, especially those affecting compliance with trial
requirements or which are considered relevant for the evaluation of the endpoints of
the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers
(gastrointestinal tract, skin) or laboratory abnormality that may increase the risk
associated with trial participation or trial drug administration, and in the judgment
of the investigator would make the patient inappropriate for entry into the trial.

- Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment,
or planned surgical procedures during the trial period.

- Patients with personal or family history of QT prolongation and/or long QT syndrome,
or prolonged QTcF at baseline (> 480 ms).

- Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension,
unstable angina, history of infarction within past 6 months, congestive heart failure
> NYHA II).

Uncontrolled hypertension defined as: Blood pressure in rested and relaxed condition >= 140
mmHg, systolic or >= 90 mmHg diastolic (with or without medication), measured according to
Appendix 10.2.

- LVEF < 50%

- History of severe hemorrhagic or thromboembolic event in the past 12 months (excluding
central venous catheter thrombosis and peripheral deep vein thrombosis).

- Known inherited predisposition to bleeding or to thrombosis in the opinion of the
investigator.

- Patient with brain metastases that are symptomatic and/or require therapy.

- Patients who require full-dose anticoagulation (according to local guidelines).

- No Vitamin K antagonist and other anticoagulation allowed; LMWH allowed only for
prevention not for curative treatment.

- History of pneumonitis (non-infectious) within the last 5 years

- Patients who are under judicial protection and patients who are legally
institutionalized.

- Patients unable or unwilling to comply with protocol

- Previous enrolment in this trial.

- Chronic alcohol or drug abuse or any condition that, in the investigator's opinion,
makes them an unreliable trial patient or unlikely to complete the trial.

- Women who are pregnant, nursing, or who plan to become pregnant in the trial

- UncontrolledSymptomatic pleural effusion, pericardial effusion, or ascites

- Prior treatment with any antiangiogenic treatment (e.g. bevacizumab, cediranib,
aflibercept, vandetanib, XL-184, sunitinib, etc) except for sorafenib and lenvatinib
in 2nd line HCC cohort (Cohort F)

- Has received a live vaccine within 30 days prior to the first dose of study drug

- Patients with known active second malignancy other than non-melanoma skin cancers,
non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular
carcinoma in situ of the breast. Patients are not considered to have a currently
active malignancy if they have completed anticancer therapy and have been disease free
for greater than 2 years prior to screening

- Further exclusion criteria apply

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris Obrien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Peninsula & South Eastern Oncology Group - Frankston
Recruitment hospital [5] 0 0
Cabrini Malvern Hospital - Malvern
Recruitment hospital [6] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment postcode(s) [5] 0 0
3144 - Malvern
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Utah
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia
Country [7] 0 0
France
State/province [7] 0 0
Dijon
Country [8] 0 0
France
State/province [8] 0 0
Marseille Cedex 5
Country [9] 0 0
France
State/province [9] 0 0
Paris
Country [10] 0 0
France
State/province [10] 0 0
Rennes Cedex
Country [11] 0 0
France
State/province [11] 0 0
Saint-Herblain
Country [12] 0 0
France
State/province [12] 0 0
Strasbourg
Country [13] 0 0
Germany
State/province [13] 0 0
Augsburg
Country [14] 0 0
Germany
State/province [14] 0 0
Dresden
Country [15] 0 0
Germany
State/province [15] 0 0
Frankfurt am Main
Country [16] 0 0
Germany
State/province [16] 0 0
Heidelberg
Country [17] 0 0
Germany
State/province [17] 0 0
Mainz
Country [18] 0 0
Germany
State/province [18] 0 0
Regensburg
Country [19] 0 0
Germany
State/province [19] 0 0
Tübingen
Country [20] 0 0
Hong Kong
State/province [20] 0 0
Hong Kong
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seongnam
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
Poland
State/province [23] 0 0
Gdansk
Country [24] 0 0
Poland
State/province [24] 0 0
Lublin
Country [25] 0 0
Poland
State/province [25] 0 0
Poznan
Country [26] 0 0
Poland
State/province [26] 0 0
Szczecin
Country [27] 0 0
Poland
State/province [27] 0 0
Warszawa
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Moscow
Country [29] 0 0
Russian Federation
State/province [29] 0 0
St. Petersburg
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Volgograd
Country [31] 0 0
Spain
State/province [31] 0 0
Barcelona
Country [32] 0 0
Spain
State/province [32] 0 0
Valencia
Country [33] 0 0
Taiwan
State/province [33] 0 0
Tainan
Country [34] 0 0
Taiwan
State/province [34] 0 0
Taipei
Country [35] 0 0
Ukraine
State/province [35] 0 0
Dnipropetrovks
Country [36] 0 0
Ukraine
State/province [36] 0 0
Kyiv
Country [37] 0 0
Ukraine
State/province [37] 0 0
Lutsk
Country [38] 0 0
Ukraine
State/province [38] 0 0
Vinnytsia
Country [39] 0 0
United Kingdom
State/province [39] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
PART 1:

Primary objective:

- To determine the Recommended Phase 2 Dose (RP2D) of BI 836880 in combination with BI 754091
in patients with locally advanced or metastatic non-squamous NSCLC who progressed during or
after first line (in case of checkpoint inhibitor naïve patients) platinum-based therapy and
patients who relapsed after completion of at least 2 cycles (in case of checkpoint inhibitor
relapsing patients) of platinum-based chemotherapy and a checkpoint inhibitor treatment
(monotherapy or in combination with chemotherapy).

Secondary objective:

- To provide safety data

- To evaluate the basic pharmacokinetics of BI 836880 and BI 754091 during combination
therapy after the first and fourth infusion cycle.

PART 2:

Primary objective:

- To assess anti-tumour activity of BI 836880 in combination with BI 754091 in patients with
locally advanced or metastatic non-squamous NSCLC and other solid tumors

Secondary objective:

- To provide safety data and further investigate clinical efficacy including disease
control (DC), duration of objective response (DoR), progression free survival (PFS), and
tumour shrinkage

- To evaluate the basic pharmacokinetics of BI 836880 and BI 754091 during combination
therapy after the first infusion cycle.
Trial website
https://clinicaltrials.gov/show/NCT03468426
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Boehringer Ingelheim
Address 0 0
Country 0 0
Phone 0 0
1-800-243-0127
Fax 0 0
Email 0 0
clintriage.rdg@boehringer-ingelheim.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03468426