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

  • STATUS
    Recruiting
  • End date
    Jun 19, 2023
  • participants needed
    305
  • sponsor
    Boehringer Ingelheim
Updated on 26 November 2021
lung cancer
pembrolizumab
advanced cancer
cancer treatment
primary cancer
neuropathy
antineoplastic agents
glioblastoma multiforme
alopecia
solid neoplasm
platinum-based chemotherapy
immunostimulants

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.

Details
Condition Cancer, Cancer/Tumors, Ewing's Family Tumors, Cancer (Pediatric), Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Neoplasms, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer, Non-squamous, Non-Small-Cell Lung Cancer
Treatment BI 836880, BI 754091, ezabenlimab
Clinical Study IdentifierNCT03468426
SponsorBoehringer Ingelheim
Last Modified on26 November 2021

Eligibility

Yes No Not Sure

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

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note