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AzTrials

NeoplasmsPhase 1NCT03964233

A Study in Patients With Different Types of Advanced Cancer (Solid Tumors) to Test Different Doses of BI 907828 (Brigimadlin) in Combination With BI 754091 (Ezabenlimab) and BI 754111 or BI 907828 (Brigimadlin) in Combination With BI 754091 (Ezabenlimab)

A Phase 1 study testing BI 907828, ezabenlimab and BI 754111 in people with Neoplasms, run by Boehringer Ingelheim at 23 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study has 2 parts. The first part of the study is done. The first part was open to adults with different types of advanced cancer (solid tumors). The second part is open to people with specific types of soft tissue sarcoma, advanced lung cancer, and cancer in the stomach, bladder or bile ducts. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
BI 907828, ezabenlimab and BI 754111
Could I receive a placebo?
No, everyone receives an active treatment
How many people
119 participants
Where
23 sitesin 11 countries
Study dates
20 Jun 2019to 6 Feb 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All cohorts:
  • Provision of signed and dated, written informed consent form ICF in accordance with International Council on Harmonization-Good Clinical Practice (ICH-GCP)and local legislation prior to any trial-specific procedures, sampling, or analyses.
  • Male or female ≥18 years old at the time of signature of the ICF.
  • ECOG performance status of 0 or 1.
  • Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement.
  • Patients with radiologically documented disease progression or relapse during or after all standard of care treatments. Patients who are not eligible to receive standard of care treatments, and for whom no proven treatments exist, are eligible.
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  • Previous treatment with an anti-PD-1/PD-L1 mAb is allowed as long as the last administration of the anti-PD-1/PD-L1 mAb on the previous treatment occurred a minimum of 28 days prior to the first administration of study treatment.
  • Patient must be willing to participate in the blood sampling for the Pharmacokinetics (PK), Pharmacodynamics (PD), biomarker, and PGx analyses.
  • Adequate organ function defined as all of the following (all screening labs should be performed locally within 10 days of treatment initiation):
  • Hematological
  • Absolute neutrophil count - ≥1.5 x 10^9/L
  • Platelets - ≥100 x 10^9/L
  • Hemoglobin 0 ≥8.5 g/dL or ≥5.3 mmol/L or ≥ 85 g/L
  • Hepatic
  • Total bilirubin ≤ 1,5 times the upper limit of normal (ULN), (patients with Gilbert's syndrome, total bilirubin must be < 3 x ULN)
  • Aspartate Transaminase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN OR ≤5 x ULN for patients with liver metastases
  • Renal
  • --- Creatinine - ≤1.5 x ULN - Patients may enter if creatinine is >1.5 x ULN and estimated glomerular filtration rate (eGFR) >50 mL/min (assessed by Chronic Kidney Disease Epidemiology [CKDEPI] Collaboration equation); confirmation of eGFR is only required when creatinine is >1.5 X ULN
  • Coagulation --- International Normalised Ratio (INR) or Prothrombin Time (PT). Activated Partial Thromboplastin Time (aPTT) - ≤1.5 x institutional ULN. Patients taking low dose warfarin must have their INR followed closely and according to institutional guidelines
  • Women of childbearing potential (WOCBP, defined as female patients who are premenopausal or who had no cessation of menses within 12 months without an alternative medical cause, but not including female patients who are permanently sterilized) and men able to father a child must be ready and able to use two medically acceptable 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 beginning at screening, during trial participation. A list of contraception methods meeting these criteria is provided in the patient information.
  • Phase Ia (dose escalation part):
  • Patients with a confirmed diagnosis of unresectable, advanced and/or metastatic solid tumors (any type) irrespective of the TP53 mutation status,
  • Patient with either evaluable or non-evaluable disease.
  • Availability and willingness to provide a sample of archival Formalin-fixed paraffin embedded (FFPE) tumor tissue material
  • Phase Ia (Expansion Cohort):
  • Patients with MDM2 amplified tumors and TP53 wild type status confirmed on tumor tissue
  • At least one target lesion that can be accurately measured per RECIST 1.1. In patients who only have one target lesion, the baseline imaging must be performed at least two weeks after any biopsy of the target lesion.
  • Phase Ib (dose expansion part):
  • At least one target lesion that can be accurately measured per RECIST 1.1. In patients who only have one target lesion, the baseline imaging must be performed at least two weeks after any biopsy of the target lesion.
  • Patients with TP53 wild-type status confirmed on tumor tissue. Provision of fresh tissue biopsy at screening (may be omitted if patient has archival tissue within 12 months prior to enrolment) and willingness to provide fresh tissue biopsy on study, if safe and feasible on either occasion
  • Expansion cohorts:
  • Cohort 1: Patients with unresectable, advanced and/or metastatic TP53 wt one line of systemic medical treatment in the advanced and/or metastatic setting: Liposarcoma excluding dedifferentiated liposarcoma, Undifferentiated pleomorphic sarcoma, Myxofibrosarcoma, Synovial sarcoma, Leiomyosarcoma
  • Cohort 2: Patients with unresectable, advanced and/or metastatic TP53 wt MDM2-amplified tumors as listed below, who received at least one line of systemic medical treatment in the advanced and/or metastatic setting: NSCLC (patients with NSCLC harboring genomic aberrations for which approved targeted therapy is approved and available, must have received such prior treatment), Gastric adenocarcinoma, Urothelial carcinoma, Biliary tract carcinoma (including cholangiocarcinoma, intra-and extrahepatic biliary tree, gall bladder and ampulla of vater)

Who cannot join

  • Previous administration of BI 907828 or any other MDM2-p53 or MDMX (MDM4)-p53 antagonist
  • In Phase Ib (expansion phase) and Phase Ia expansion cohort only: a documented amino-acid altering mutation in TP53 occurring in the patient's tumor.
  • Symptomatic brain metastases. Note: Patients with previously treated brain metastases may participate but treated lesions should not be used as target lesions
  • Active bleeding, significant risk of haemorrhage (e.g. previous severe gastrointestinal bleeding, previous haemorrhagic stroke at any time), or current bleeding disorder (e.g. haemophilia, von Willebrand disease)
  • Major surgery (major according to the Investigator's assessment) performed within 12 weeks prior to start of study treatment, or planned within 12 months after screening (e.g. hip replacement).
  • Any other documented active or suspected malignancy or history of malignancy within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment.
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  • Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
  • Currently enrolled in another investigational device or drug trial, or less than 4 weeks since receiving other investigational treatments. Patients who are in follow-up/observation for another clinical trial are eligible.
  • Patients who have not recovered from all clinically significant adverse events from their most recent therapy or intervention prior to study enrolment
  • Known history of human immunodeficiency virus (HIV) infection
  • Any of the following laboratory evidence of hepatitis virus infection:
  • Positive results of hepatitis B surface (HBs) antigen
  • Presence of HBc antibody together with HBV-DNA
  • Presence of hepatitis C RNA
  • Known hypersensitivity to the trial drugs or their excipients.
  • Serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal 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.
  • 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 while in the trial; female patients who do not agree to the interruption of breast feeding from the start of study treatment to within 30 days after the last study treatment.
  • History (including current) of interstitial lung disease or pneumonitis within the last 5 years.
  • History of severe hypersensitivity reactions to other monoclonal antibodies
  • Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of study treatment.
  • Active autoimmune disease or a documented history of autoimmune disease, disease, that requires systemic treatment, i.e. corticosteroids or immunosuppressive drugs, except vitiligo or resolved childhood asthma/atopyatopy, alopecia, or any chronic skin condition that does not require systemic therapy; patients with autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and/or controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible.
  • Active infection requiring systemic treatment (antibacterial, antiviral, or antifungal therapy) at start of treatment in this trial.
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc) >470 msec
  • Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block
  • Any factor that increases the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval
  • Patients with an ejection fraction (EF) <50% or the lower limit of normal of the institutional standard will be excluded. Only in cases where the Investigator (or the treating physician or both) suspects cardiac disease with negative effect on the EF, will the EF be measured during screening using an appropriate method according to local standards to confirm eligibility (e.g., echocardiogram, multi-gated acquisition scan). A historic measurement of EF no older than 6 months prior to first administration of study drug can be accepted provided that there is clinical evidence that the EF value has not worsened since this measurement in the opinion of the Investigator or of the treating physician or both.

Trial locations and contacts

23 sites in 11 countries.

23 sites in 11 countries

United States9 sites

  • University Cancer and Blood Center

    Athens, Georgia, 30607

  • NEXT Virginia

    Fairfax, Virginia, 22031

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • NEXT Oncology-Irving-69444

    Irving, Texas, 75039

  • Yale Cancer Center

    New Haven, Connecticut, 06511

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • NEXT Oncology-San Antonio-65273

    San Antonio, Texas, 78229

  • Sarcoma Oncology Center

    Santa Monica, California, 90403

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

France3 sites

  • INS Bergonie

    Bordeaux, 33000

  • CTR Leon Berard

    Lyon, 69373

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Germany2 sites

  • Universitätsklinikum Frankfurt

    Frankfurt, 60590

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

Spain2 sites

  • Hospital Universitari Vall D Hebron

    Barcelona, 08035

  • Hospital Clínico San Carlos

    Madrid, 28040

Other trials in Spain

Australia1 site

  • Linear Clinical Research

    Nedlands, Western Australia, 6009

Other trials in Australia

Belgium1 site

  • UZ Leuven

    Leuven, 3000

Other trials in Belgium

Hungary1 site

  • Central Hospital of Northern Pest - Military Hospital

    Budapest, 1062

Other trials in Hungary

Japan1 site

  • National Cancer Center Hospital

    Tokyo, Chuo-ku, 104-0045

Other trials in Japan

Netherlands1 site

  • Universitair Medisch Centrum Groningen

    Groningen, 9713 GZ

Other trials in Netherlands

Singapore1 site

  • National Cancer Centre Singapore

    Singapore, 168583

Other trials in Singapore

United Kingdom1 site

  • The Royal Marsden Hospital, Chelsea

    London, SW3 6JJ

Other trials in United Kingdom

About this study

Official title: A Phase Ia/Ib, Open Label, Dose-escalation Study of the Combination of BI 907828 (Brigimadlin) With BI 754091 (Ezabenlimab) and BI 754111 and the Combination of BI 907828 (Brigimadlin) With BI 754091(Ezabenlimab) Followed by Expansion Cohorts, in Patients With Advanced Solid Tumors

This study has 2 parts. The first part of the study is done. The first part was open to adults with different types of advanced cancer (solid tumors). The second part is open to people with specific types of soft tissue sarcoma, advanced lung cancer, and cancer in the stomach, bladder or bile ducts.

The participants get a combination of 2 medicines called brigimadlin (also called BI 907828) and ezabenlimab (also called BI 754091). Brigimadlin is a so-called MDM2 inhibitor that is being developed to treat cancer. Ezabenlimab is an antibody that may help the immune system fight cancer (immune checkpoint inhibitor). When the study started, some participants got a third medicine called BI 754111 in addition. Treatment with BI 754111 was stopped because data from another study showed no additional effect of BI 754111.

Read more

The purpose of the first part of the study was to find out the highest dose of brigimadlin that the participants could tolerate in combination with ezabenlimab. This dose is used in the second part of the study.

The purpose of the second part is to see whether the combination of brigimadlin with ezabenlimab is able to make tumors shrink.

The participants are in the study as long as they benefit from treatment and can tolerate it.

Ezabenlimab treatment is limited to 2 years. During this time, they get infusions of ezabenlimab, and take tablets with brigimadlin every 3 weeks. The doctors check how many participants have health problems during the study. The doctors also monitor the size of the tumor.

Conditions
Neoplasms
Being tested
BI 907828, ezabenlimab, BI 754111
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BI 907828Drug

    Also called Brigimadlin

    Film-coated tablets

  • ezabenlimabDrug

    Also called BI 754091

    Solution for infusion

  • BI 754111Drug

    Solution for infusion

Study groups in NCT03964233
Study groupRoleWhat they receive
Dose Escalation - BI 907828 + ezabenlimabExperimentalAll neoplasms
Receives: Drug: BI 907828; Drug: ezabenlimab
Dose Expansion - Cohort 1 BI 907828 + ezabenlimabExperimentalNot described
Receives: Drug: BI 907828; Drug: ezabenlimab
Dose Expansion - Cohort 2 - BI 907828 + ezabenlimabExperimentalNot described
Receives: Drug: BI 907828; Drug: ezabenlimab
Dose Escalation - BI 907828 + ezabenlimab + BI 754111ExperimentalAll neoplasms
Receives: Drug: BI 907828; Drug: ezabenlimab; Drug: BI 754111

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase Ia - maximum tolerated dose (MTD) of brigimadlin (BI 907828) in combination with ezabenlimab based on the number of patients with dose limiting toxicities (DLTs) during the first treatment cycle

    Measured: Up to 21 Days

  2. Phase Ib - Objective response (OR)

    Measured: Up to 24 months

  3. Phase Ib - Progression free survival

    Measured: Up to 24 months

Secondary outcomes (7)

  1. Phase Ia - Cmax : Maximum measured plasma concentration of brigimadlin (BI 907828) and ezabenlimab (during the first cycle)

    Measured: Up to 21 Days

  2. Phase Ia - AUC0-tz: Area under the concentration-time curve in plasma for brigimadlin (BI 907828) and ezabenlimab over the time interval from 0 to the last quantifiable time point (during the first cycle)

    Measured: Up to 21 Days

  3. Phase Ia - Number of patients with DLTs observed during the entire treatment period

    Measured: Up to 24 months

  4. Phase Ib - Objective Response (OR)

    Measured: Up to 24 months

  5. Phase Ib - Disease control (DC)

    Measured: Up to 24 months

  6. Phase Ib - Number of patients with DLTs

    Measured: Up to 2 years

  7. Phase Ib - Overall survival (OS)

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 May 2019
  2. Study start20 Jun 2019
  3. Primary completion5 Sep 2024
  4. Study completion6 Feb 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
119 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03964233
Sponsor's protocol ID
1403-0002
Other IDs
2019-001173-84, 2019
Status last verified
Feb 2026
First submitted
24 May 2019
Last updated
18 Feb 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BI 907828, ezabenlimab and BI 754111 in people with Neoplasms, run by Boehringer Ingelheim at 23 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, France, Germany, Spain, Australia and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase Ia - maximum tolerated dose (MTD) of brigimadlin (BI 907828) in combination with ezabenlimab based on the number of patients with dose limiting toxicities (DLTs) during the first treatment cycle (time frame: Up to 21 Days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03964233.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2026.

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