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

Brightline-2: A Phase IIa/IIb, Open-label, Single-arm, Multi-centre Trial of BI 907828 (Brigimadlin) 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: Terminated
• Conditions: Lung Neoplasms; Pancreatic Neoplasms; Bladder Cancer; Solid Tumors; Biliary Tract Cancer
• Intervention / Treatment: Drug: brigimadlin

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital-Randwick-66496
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • ICON-South Brisbane-69267
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
• Austria
  • Linz, Austria, 4020
    • Ordensklinikum Linz GmbH - Barmherzige Schwestern
  • Wiener Neustadt, Austria, 2700
    • LK Wiener Neustadt
• Belgium
  • Edegem, Belgium, 2650
    • Edegem - UNIV UZ Antwerpen
  • Ghent, Belgium, 9000
    • Universitair Ziekenhuis Gent
• France
  • Dijon, France, 21079
    • CTR Georges-François Leclerc
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus Dresden
  • Frankfurt, Germany, 60488
    • Krankenhaus Nordwest, Frankfurt
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • München, Germany, 81377
    • Klinikum Der Universität München AöR
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm
• Japan
  • Chiba, Kashiwa, Japan, 277-8577
    • National Cancer Center Hospital East
  • Kanagawa, Yokohama, Japan, 241-8515
    • Kanagawa Cancer Center
  • Miyagi, Sendai, Japan, 980-8574
    • Tohoku University Hospital
  • Osaka, Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Tokyo, Chuo-ku, Japan, 104-0045
    • National Cancer Center Hospital
  • Tokyo, Koto-ku, Japan, 135-8550
    • Japanese Foundation for Cancer Research
  • Yamaguchi, Ube, Japan, 755-8505
    • Yamaguchi University Hospital
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11481
    • King Abdul Aziz Medical City
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital-Singapore-42005
• South Africa
  • KwaZulu, South Africa, 4126
    • Rainbow Oncology
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebrón
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario De Valencia
• Switzerland
  • Bern, Switzerland, 3010
    • University Hospital Bern
  • Geneva, Switzerland, CH-1211
    • University Hospital Geneva
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 404327
    • China Medical University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 106
    • National Taiwan University Cancer Center
• Thailand
  • Hat Yai, Thailand, 90110
    • Songklanagarind hospital
  • Muang, Thailand, 40002
    • Srinagarind Hospital
• United Kingdom
  • London, United Kingdom, WC1E 6AG
    • University College Hospital
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Southern Cancer Center
  • Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona
  • California
    • Los Angeles, California, United States, 90033-9173
      • University of Southern California
    • Palo Alto, California, United States, 94305
      • Stanford Cancer Institute
    • Santa Rosa, California, United States, 95403
      • Providence Medical Foundation-Santa Rosa -69764
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers-Lone Tree-69498
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20016
      • Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute, Downtown
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists-Omaha-69066
  • New York
    • Mineola, New York, United States, 11501
      • Perlmutter Cancer Center at NYU Langone Hospital - Long Island
    • New York, New York, United States, 10016
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
    • New York, New York, United States, 10022
      • Memorial Sloan-Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oncology Associates of Oregon, PC
    • Portland, Oregon, United States, 97239
      • Oregon Health and Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

1

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)	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)	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)	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)	OS is defined as the time from treatment start until death from any cause.	Up to 50 months
Disease control (DC)	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		Up to 30 months
Occurrence of treatment-emergent AEs leading to trial drug discontinuation during the on-treatment period		Up to 30 months

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Yoo C, Lamarca A, Choi HJ, Vogel A, Pishvaian MJ, Goyal L, Ueno M, Marten A, Teufel M, Geng L, Morizane C. Brightline-2: a phase IIa/IIb trial of brigimadlin (BI 907828) in advanced biliary tract cancer, pancreatic ductal adenocarcinoma or other solid tumors. Future Oncol. 2024;20(16):1069-1077. doi: 10.2217/fon-2023-0963. Epub 2024 Jan 12.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2022
• Primary Completion (Actual): September 25, 2025
• Study Completion (Actual): September 25, 2025

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): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Digestive System Neoplasms; Digestive System Diseases; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Biliary Tract Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Urologic Neoplasms; Urinary Bladder Diseases; Biliary Tract Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Urinary Bladder Neoplasms; brigimadlin
• Other Study ID Numbers: 1403-0011; 2022-001500-18 (EudraCT Number); U1111-1292-3392 (Registry Identifier: WHO International Clinical Trials Registry Platform (ICTRP)); 2023-506369-79-00 (Other Identifier: CTIS)

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