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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03468426

Registration number

NCT03468426

Ethics application status

Date submitted

8/03/2018

Date registered

16/03/2018

Date last updated

3/04/2024

Titles & IDs

Public title

A Study to Test Different Doses of BI 836880 Combined With Ezabenlimab 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 Ezabenlimab 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]

2017-001378-41

Secondary ID [2]

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

Neoplasms

Condition category

Condition code

Cancer

Lung - Mesothelioma

Cancer

Lung - Non small cell

Cancer

Lung - Small cell

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - BI 836880
Treatment: Drugs - ezabenlimab

Experimental: BI 836880 + ezabenlimab -

Treatment: Drugs: BI 836880
intra-venous infusion

Treatment: Drugs: ezabenlimab
intra-venous infusion

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part 1: Number of patients with Dose Limiting Toxicities (DLTs) within the first cycle of treatment

Timepoint [1]

Up to 3 weeks

Primary outcome [2]

Part 2: Objective response

Timepoint [2]

Up to 3 years

Secondary outcome [1]

Part 1: Adverse events (AEs), drug related AEs, drug related AEs leading to discontinuation during treatment period

Timepoint [1]

Up to 294 days

Secondary outcome [2]

Part 1: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours (AUC 0-504h) after the first infusion cycle

Timepoint [2]

Up to 504 hours after first infusion cycle

Secondary outcome [3]

Part 1: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours (AUC 0-504h) after the fourth infusion cycle

Timepoint [3]

Up to 504 hours after fourth infusion cycle

Secondary outcome [4]

Part 1: Maximum measured concentration of the analyte in plasma (Cmax)

Timepoint [4]

Up to 12 weeks

Secondary outcome [5]

Part 1: Time from dosing to maximum measured concentration of the analyte in plasma (tmax)

Timepoint [5]

Up to 12 weeks

Secondary outcome [6]

Part 2: Adverse events (AEs), drug related AEs, drug related AEs leading to discontinuation during treatment period

Timepoint [6]

Up to 294 days

Secondary outcome [7]

Part 2: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours (AUC 0-504h) after the first infusion cycle

Timepoint [7]

Up to 504 hours after first infusion cycle

Secondary outcome [8]

Part 2: Time from dosing to maximum measured concentration of the analyte in plasma (tmax)

Timepoint [8]

Up to 12 weeks

Secondary outcome [9]

Part 2: Maximum measured concentration of the analyte in plasma (Cmax)

Timepoint [9]

Up to 12 weeks

Secondary outcome [10]

Part 2: Disease control (DC)

Timepoint [10]

Up to 3 years

Secondary outcome [11]

PART 2: Duration of objective response (DoR)

Timepoint [11]

Up to 3 years

Secondary outcome [12]

Part 2: Progression-free survival (PFS)

Timepoint [12]

Up to 3 years

Secondary outcome [13]

Part 2: Tumour shrinkage (in millimeters)

Timepoint [13]

Up to 3 years

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 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 where brain lesions are allowed), that can be accurately measured per RECIST
version 1.1 or Response Assessment in Neuro-Oncology (RANO)

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

- 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

Sex

Both males and females

Can healthy volunteers participate?

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 (e.g.
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). In case of CPIs combination, they need to be approved by the local
regulatory agencies; for e.g., 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

Active, not recruiting

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

3/05/2018

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

1/11/2024

Actual

Sample size

Target

Accrual to date

Final

252

Recruitment in Australia

Recruitment state(s)

NSW,VIC

Recruitment hospital [1]

Royal North Shore Hospital - St Leonards

Recruitment hospital [2]

Westmead Hospital - Westmead

Recruitment hospital [3]

Peninsula & South Eastern Oncology Group - Frankston

Recruitment hospital [4]

Alfred Hospital - Melbourne

Recruitment postcode(s) [1]

2065 - St Leonards

Recruitment postcode(s) [2]

2145 - Westmead

Recruitment postcode(s) [3]

3199 - Frankston

Recruitment postcode(s) [4]

3004 - Melbourne

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

Alabama

Country [2]

United States of America

State/province [2]

California

Country [3]

United States of America

State/province [3]

Georgia

Country [4]

United States of America

State/province [4]

Massachusetts

Country [5]

United States of America

State/province [5]

Utah

Country [6]

United States of America

State/province [6]

Virginia

Country [7]

France

State/province [7]

Dijon

Country [8]

France

State/province [8]

Marseille

Country [9]

France

State/province [9]

Paris

Country [10]

France

State/province [10]

Rennes

Country [11]

France

State/province [11]

Saint-Herblain

Country [12]

France

State/province [12]

Strasbourg

Country [13]

Germany

State/province [13]

Augsburg

Country [14]

Germany

State/province [14]

Dresden

Country [15]

Germany

State/province [15]

Frankfurt am Main

Country [16]

Germany

State/province [16]

Mainz

Country [17]

Germany

State/province [17]

Regensburg

Country [18]

Hong Kong

State/province [18]

Hong Kong

Country [19]

Korea, Republic of

State/province [19]

Seongnam

Country [20]

Korea, Republic of

State/province [20]

Seoul

Country [21]

Poland

State/province [21]

Gdansk

Country [22]

Poland

State/province [22]

Lublin

Country [23]

Poland

State/province [23]

Otwock

Country [24]

Poland

State/province [24]

Poznan

Country [25]

Poland

State/province [25]

Szczecin

Country [26]

Russian Federation

State/province [26]

Moscow

Country [27]

Russian Federation

State/province [27]

St. Petersburg

Country [28]

Russian Federation

State/province [28]

Volgograd

Country [29]

Spain

State/province [29]

Barcelona

Country [30]

Spain

State/province [30]

Valencia

Country [31]

Taiwan

State/province [31]

Tainan

Country [32]

Taiwan

State/province [32]

Taipei

Country [33]

Ukraine

State/province [33]

Dnipropetrovks

Country [34]

Ukraine

State/province [34]

Kyiv

Country [35]

Ukraine

State/province [35]

Lutsk

Country [36]

Ukraine

State/province [36]

Vinnytsia

Country [37]

United Kingdom

State/province [37]

London

Funding & Sponsors

Primary sponsor type

Commercial sector/Industry

Name

Boehringer Ingelheim

Address

Country

Ethics approval

Ethics application status

Summary

Brief summary

This study has 2 parts. The first part was open to adults with advanced non-small cell lung
cancer. The second part was open also to adults with other types of advanced cancer of the
lung, brain, skin, and liver. After early encouraging results, more people with liver cancer
can now take part in the study. The participants get a combination of two medicines called BI
836880 and ezabenlimab.

BI 836880 is a type of an antibody that blocks new blood vessel formation. New blood vessels
are needed by the tumour to continue growing. Ezabenlimab is an antibody that may help the
immune system fight cancer (immune checkpoint inhibitor).

The purpose of the first part of the study was to find out the highest dose of the BI 836880
that the participants can tolerate in combination with BI 754091. After the best dose of BI
836880 for the combination with ezabenlimab was found, it is used in the second part of the
study. The purpose of the second part is to see whether the combination of BI 836880 and BI
754091 is able to make tumours shrink.

The participants are in the study as long as they benefit from and can tolerate treatment.
During this time, they get infusions of BI 836880 and ezabenlimab every 3 weeks. The doctors
also regularly check the general health of the participants.

Trial website

https://clinicaltrials.gov/ct2/show/NCT03468426

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03468426