Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder

March 18, 2024 updated by: Boehringer Ingelheim

Brightline-2: A Phase IIa/IIb, Open-label, Single-arm, Multi-centre Trial of Brigimadlin (BI 907828) for Treatment of Patients With Locally Advanced / Metastatic, MDM2 Amplified, TP53 Wild-type Biliary Tract Adenocarcinoma, Pancreatic Ductal Adenocarcinoma, or Other Selected Solid Tumours

This study is open to adults with advanced cancer in the biliary tract, pancreas, lung, or bladder. This is a study for people for whom previous treatment was not successful or no treatment exists.

The purpose of this study is to find out whether a medicine called BI 907828 helps people with cancer in the biliary tract, pancreas, lung, or bladder. BI 907828 is a so-called MDM2 inhibitor that is being developed to treat cancer. All participants take BI 907828 as a tablet once every 3 weeks. Participants may continue to take BI 907828 as long as they benefit from treatment and can tolerate it. They visit the study site regularly. At the study site, doctors regularly check the size of the tumour and whether it has spread to other parts of the body. The doctors also regularly check participants' health and take note of any unwanted effects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

155

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Additional US locations available on demand. Please contact for options.
  • Phone Number: 1-800-243-0127

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
  • Austria
      • Wiener Neustadt, Austria, 2700
  • Belgium
      • Edegem, Belgium, 2650
      • Gent, Belgium, 9000
  • France
      • Bordeaux, France, 33000
      • Clichy, France, 92110
      • Dijon, France, 21079
        • Recruiting
        • CTR Georges-François Leclerc
        • Contact:
      • Lyon, France, 69437
      • Villejuif, France, 94805
  • Germany
      • Dresden, Germany, 01307
        • Recruiting
        • Universitätsklinikum Carl Gustav Carus Dresden
        • Contact:
      • Frankfurt, Germany, 60488
      • Hannover, Germany, 30625
      • München, Germany, 81377
        • Recruiting
        • Klinikum der Universität München - Campus Großhadern
        • Contact:
      • Ulm, Germany, 89081
  • Japan
      • Chiba, Kashiwa, Japan, 277-8577
        • Recruiting
        • National Cancer Center Hospital East
        • Contact:
      • Kanagawa, Yokohama, Japan, 241-8515
      • Miyagi, Sendai, Japan, 980-8574
        • Recruiting
        • Tohoku University Hospital
        • Contact:
      • Osaka, Osaka, Japan, 541-8567
        • Recruiting
        • Osaka International Cancer Institute
        • Contact:
      • Tokyo, Chuo-ku, Japan, 104-0045
        • Recruiting
        • National Cancer Center Hospital
        • Contact:
      • Tokyo, Koto-ku, Japan, 135-8550
        • Recruiting
        • Japanese Foundation for Cancer Research
        • Contact:
      • Yamaguchi, Ube, Japan, 755-8505
        • Recruiting
        • Yamaguchi University Hospital
        • Contact:
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
      • Seoul, Korea, Republic of, 05505
      • Seoul, Korea, Republic of, 135-710
      • Seoul, Korea, Republic of, 03722
  • Singapore
      • Singapore, Singapore, 119074
  • Spain
      • Barcelona, Spain, 08035
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
        • Contact:
      • Madrid, Spain, 28040
        • Recruiting
        • Fundación Jiménez Díaz
        • Contact:
      • Valencia, Spain, 46010
        • Recruiting
        • Hospital Clinico de Valencia
        • Contact:
  • Switzerland
      • Bern, Switzerland, 3010
        • Recruiting
        • University Hospital Bern/Inselspital Bern
        • Contact:
      • Genève 14, Switzerland, CH-1211
        • Recruiting
        • University Hospital Geneva
        • Contact:
  • Taiwan
      • Kaohsiung, Taiwan, 80756
        • Recruiting
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
        • Contact:
      • Taichung, Taiwan, 404
        • Recruiting
        • China Medical University Hospital
        • Contact:
      • Taipei, Taiwan, 11217
        • Recruiting
        • Taipei Veterans General Hospital
        • Contact:
      • Taipei, Taiwan, 106
        • Recruiting
        • National Taiwan University Cancer Center
        • Contact:
  • Thailand
      • Bangkok, Thailand, 10210
        • Recruiting
        • Chulabhorn Hospital
        • Contact:
      • Chiang Mai, Thailand, 50200
        • Recruiting
        • Maharaj Nakom Chiangmai Hospital
        • Contact:
      • Hat Yai, Thailand, 90110
        • Recruiting
        • Songklanagarind Hospital
        • Contact:
      • Muang, Thailand, 40002
        • Recruiting
        • Srinagarind Hospital
        • Contact:
  • United Kingdom
      • London, United Kingdom, WC1E 6AG
  • United States
    • Alabama
      • Mobile, Alabama, United States, 36608
    • Arizona
      • Tucson, Arizona, United States, 85719
    • California
      • Beverly Hills, California, United States, 90212
      • Los Angeles, California, United States, 90033-9173
      • Palo Alto, California, United States, 94305
      • Santa Rosa, California, United States, 95403
    • Colorado
      • Lone Tree, Colorado, United States, 80124
    • District of Columbia
      • Washington, District of Columbia, United States, 20016
        • Recruiting
        • Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital
        • Contact:
    • Kentucky
      • Louisville, Kentucky, United States, 40202
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
    • Nebraska
      • Omaha, Nebraska, United States, 68130
    • New York
      • Mineola, New York, United States, 11501
        • Recruiting
        • Perlmutter Cancer Center at NYU Langone Hospital - Long Island
        • Contact:
      • New York, New York, United States, 10016
        • Recruiting
        • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
        • Contact:
      • New York, New York, United States, 10022
    • Oregon
      • Portland, Oregon, United States, 97239
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center
        • Contact:
    • Wisconsin
      • Madison, Wisconsin, United States, 53792

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of a solid tumour which meets the criteria for an open trial cohort:

    • Cohorts 1 and 1-CN (biliary tract adenocarcinoma): Locally advanced or metastatic biliary tract adenocarcinoma (intra- and extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary cancer).Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards; or (in the opinion of the investigator) patients are unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
    • Cohort 2 (pancreatic ductal adenocarcinoma): Locally advanced or metastatic pancreatic ductal adenocarcinoma. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
    • Cohort 3 (lung adenocarcinoma): Locally advanced or metastatic lung adenocarcinoma. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
    • Cohort 4 (urothelial bladder cancer): Locally advanced or metastatic urothelial bladder cancer. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
  • Written pathology report / molecular profiling report indicating Mouse double minute 2 homolog (MDM2) amplification or a copy number ≥8 and tumor protein 53 (TP53) wild-type status. This must have been confirmed with a tissue-based test. A test with liquid biopsy is not accepted.
  • Archival tissue (formalin fixed paraffin embedded [FFPE] tumour blocks or slides) must be provided for retrospective confirmation of MDM2 amplification and TP53 status.
  • Presence of at least 1 measurable target lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  • Patient must be willing to donate mandatory blood samples for the pharmacokinetics, pharmacodynamics, and biomarker analyses
  • Adequate organ function
  • All toxicities related to previous anti-cancer therapies have resolved to ≤Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 prior to trial treatment administration (except for alopecia and amenorrhea / menstrual disorders which can be of any grade and peripheral neuropathy which must be ≤CTCAE Grade 2).
  • Life expectancy ≥3 months at the start of treatment in the opinion of the investigator.
  • Provision of signed and dated, written informed consent form (ICF) in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
  • Male or female patients ≥18 years old at the time of signature of the ICF. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use 2 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, and until 6 months and 12 days after last dose for women and 102 days after last dose for men. A list of contraception methods meeting these criteria is provided in the patient information.

Exclusion Criteria:

  • Previous administration of brigimadlin (BI 907828) or any other MDM2-p53 or mouse double minute 4 (MDMX, MDM4)-p53 antagonist.
  • 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 4 weeks prior to start of trial treatment or planned within 6 months after screening (e.g. hip replacement).
  • Clinically significant previous or concomitant malignancies in the opinion of the investigator affecting the efficacy and/or outcome of the trial.
  • Patients who must or intend 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.
  • Any history of, or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the trial drug.
  • Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator's opinion, makes the patient an unreliable trial participant).

Further exclusion criteria apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: brigimadlin (BI 907828) treatment arm
Drug: brigimadlin
brigimadlin
Other Names:
  • BI 907828

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response (OR)
Time Frame: Up to 30 months
OR is defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1.
Up to 30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of objective response (DOR)
Time Frame: Up to 30 months
DOR is defined as the time from first documented confirmed objective response (OR) until the earliest date of disease progression or death among patients with confirmed objective response.
Up to 30 months
Progression-free survival (PFS)
Time Frame: Up to 30 months
PFS is defined as the time from treatment start until the earliest date of tumour progression according to RECIST version 1.1 or death from any cause, whichever occurs first.
Up to 30 months
Overall survival (OS)
Time Frame: Up to 50 months
OS is defined as the time from treatment start until death from any cause.
Up to 50 months
Disease control (DC)
Time Frame: Up to 30 months
DC is defined as a best overall response of CR, PR, or stable disease (SD) where best overall response is defined according to RECIST version 1.1.
Up to 30 months
Occurrence of treatment-emergent adverse events (AEs) during the on-treatment period
Time Frame: Up to 30 months
Up to 30 months
Occurrence of treatment-emergent AEs leading to trial drug discontinuation during the on-treatment period
Time Frame: Up to 30 months
Up to 30 months
Change from baseline in European Organisation for Research and Treatment (EORTC) Quality of Life Questionnaire (QLQ)-C30 physical functioning domain score
Time Frame: Up to 30 months
The QLQ-C30 comprises 30 questions. The QLQ-C30 incorporates both multi-items scales and single-item measures. These include 1 global health status/QoL scale, 5 functional scales, 3 symptoms scales and 6 single items to assess dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function, symptoms and financial difficulties and 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life.
Up to 30 months
Change from baseline in EORTC QLQ-C30 fatigue domain score
Time Frame: Up to 30 months
It is part of QLQ-C30 and uses 4-point scale (1=not at all to 4=very much)
Up to 30 months
Change from baseline in EORTC QLQ-C30 role functioning domain score
Time Frame: Up to 30 months
It is part of QLQ-C30 and uses 4-point scale (1=not at all to 4=very much)
Up to 30 months
Change from baseline in EORTC QLQ-BIL21 tiredness domain score
Time Frame: Up to 30 months
The QLQ-BIL21 is specific for the assessment of quality of life in patients with cholangiocarcinoma and cancer of the gallbladder. It consists of 21 questions with a 4-point scale (1=not at all to 4=very much), and the tiredness domain is part of it.
Up to 30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 25, 2022

Primary Completion (Estimated)

February 20, 2025

Study Completion (Estimated)

March 25, 2027

Study Registration Dates

First Submitted

August 22, 2022

First Submitted That Met QC Criteria

August 22, 2022

First Posted (Actual)

August 23, 2022

Study Record Updates

Last Update Posted (Actual)

March 19, 2024

Last Update Submitted That Met QC Criteria

March 18, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1403-0011
  • 2022-001500-18 (EudraCT Number)
  • U1111-1292-3392 (Registry Identifier: WHO Registry)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Once the criteria in section "Time Frame" are fulfilled, researchers can use the 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".

Furthermore, researchers can 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.

IPD Sharing Time Frame

After structured results have been posted, 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.

IPD Sharing 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 the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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