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 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
2 other identifiers
interventional
119
11 countries
23
Brief 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. 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2019
Longer than P75 for phase_1
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 24, 2019
CompletedFirst Posted
Study publicly available on registry
May 28, 2019
CompletedStudy Start
First participant enrolled
June 20, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 5, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
February 6, 2026
CompletedFebruary 18, 2026
February 1, 2026
5.2 years
May 24, 2019
February 17, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
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
Up to 21 Days
Phase Ib - Objective response (OR)
Up to 24 months
Phase Ib - Progression free survival
Up to 24 months
Secondary Outcomes (7)
Phase Ia - Cmax : Maximum measured plasma concentration of brigimadlin (BI 907828) and ezabenlimab (during the first cycle)
Up to 21 Days
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)
Up to 21 Days
Phase Ia - Number of patients with DLTs observed during the entire treatment period
Up to 24 months
Phase Ib - Objective Response (OR)
Up to 24 months
Phase Ib - Disease control (DC)
Up to 24 months
- +2 more secondary outcomes
Study Arms (4)
Dose Escalation - BI 907828 + ezabenlimab
EXPERIMENTALAll neoplasms
Dose Expansion - Cohort 1 BI 907828 + ezabenlimab
EXPERIMENTALDose Expansion - Cohort 2 - BI 907828 + ezabenlimab
EXPERIMENTALDose Escalation - BI 907828 + ezabenlimab + BI 754111
EXPERIMENTALAll neoplasms
Interventions
Film-coated tablets
Solution for infusion
Eligibility Criteria
You may qualify if:
- 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.
- 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)
- +18 more criteria
You may not qualify if:
- 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.
- 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.
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
Sarcoma Oncology Center
Santa Monica, California, 90403, United States
Yale Cancer Center
New Haven, Connecticut, 06511, United States
University Cancer and Blood Center
Athens, Georgia, 30607, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
NEXT Oncology-Irving-69444
Irving, Texas, 75039, United States
NEXT Oncology-San Antonio-65273
San Antonio, Texas, 78229, United States
NEXT Virginia
Fairfax, Virginia, 22031, United States
Linear Clinical Research
Nedlands, Western Australia, 6009, Australia
UZ Leuven
Leuven, 3000, Belgium
INS Bergonie
Bordeaux, 33000, France
CTR Leon Berard
Lyon, 69373, France
Institut Gustave Roussy
Villejuif, 94805, France
Universitätsklinikum Frankfurt
Frankfurt, 60590, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
Central Hospital of Northern Pest - Military Hospital
Budapest, 1062, Hungary
National Cancer Center Hospital
Tokyo, Chuo-ku, 104-0045, Japan
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ, Netherlands
National Cancer Centre Singapore
Singapore, 168583, Singapore
Hospital Universitari Vall D Hebron
Barcelona, 08035, Spain
Hospital Clínico San Carlos
Madrid, 28040, Spain
The Royal Marsden Hospital, Chelsea
London, SW3 6JJ, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 24, 2019
First Posted
May 28, 2019
Study Start
June 20, 2019
Primary Completion
September 5, 2024
Study Completion
February 6, 2026
Last Updated
February 18, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
- Access Criteria
- For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
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.