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

Bladder Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05512377
• Other study ID #: 1403-0011
• Secondary ID: 2023-506369-79-0
• Status: Recruiting
• Phase: Phase 2
• Start date: November 25, 2022
• Est. completion date: March 25, 2027

Study information

• Verified date: June 2024
• Source: Boehringer Ingelheim
• Contact: Boehringer Ingelheim
• Phone: 1-800-243-0127
• Email: clintriage.rdg[@]boehringer-ingelheim.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 155
• Est. completion date: March 25, 2027
• Est. primary completion date: June 17, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Biliary Tract Cancer
• Biliary Tract Neoplasms
• Bladder Cancer
• Lung Neoplasms
• Neoplasms
• Pancreatic Neoplasms
• Solid Tumors

Intervention

Drug:
• brigimadlin
brigimadlin

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Austin Health	Heidelberg	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	ICON	South Brisbane	Queensland
Austria	LK Wiener Neustadt	Wiener Neustadt
Belgium	Edegem - UNIV UZ Antwerpen	Edegem
Belgium	UNIV UZ Gent	Gent
France	INS Bergonie	Bordeaux
France	HOP Beaujon	Clichy
France	CTR Georges-François Leclerc	Dijon
France	HOP Edouard Herriot	Lyon
France	INS Gustave Roussy	Villejuif
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Krankenhaus Nordwest, Frankfurt	Frankfurt
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Klinikum der Universität München - Campus Großhadern	München
Germany	Universitätsklinikum Ulm	Ulm
Japan	National Cancer Center Hospital East	Chiba, Kashiwa
Japan	Kanagawa Cancer Center	Kanagawa, Yokohama
Japan	Tohoku University Hospital	Miyagi, Sendai
Japan	Osaka International Cancer Institute	Osaka, Osaka
Japan	National Cancer Center Hospital	Tokyo, Chuo-ku
Japan	Japanese Foundation for Cancer Research	Tokyo, Koto-ku
Japan	Yamaguchi University Hospital	Yamaguchi, Ube
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Singapore	National University Hospital	Singapore
South Africa	Rainbow Oncology	KwaZulu
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Clínico de Valencia	Valencia
Switzerland	University Hospital Bern/Inselspital Bern	Bern
Switzerland	University Hospital Geneva	Genève 14
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Cancer Center	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Thailand	Chulabhorn Hospital	Bangkok
Thailand	Maharaj Nakom Chiangmai Hospital	Chiang Mai
Thailand	Songklanagarind Hospital	Hat Yai
Thailand	Srinagarind Hospital	Muang
United Kingdom	University College Hospital	London
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Precision NextGen Oncology	Beverly Hills	California
United States	Cleveland Clinic	Cleveland	Ohio
United States	Oncology Associates of Oregon, PC	Eugene	Oregon
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Rocky Mountain Cancer Centers	Lone Tree	Colorado
United States	University of Southern California	Los Angeles	California
United States	Norton Cancer Institute, Downtown	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	Perlmutter Cancer Center at NYU Langone Hospital - Long Island	Mineola	New York
United States	Southern Cancer Center	Mobile	Alabama
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Stanford Cancer Institute	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health and Sciences University	Portland	Oregon
United States	Providence Medical Foundation	Santa Rosa	California
United States	University of Arizona	Tucson	Arizona
United States	Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  France,  Germany,  Japan,  Korea, Republic of,  Singapore,  South Africa,  Spain,  Switzerland,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Overall survival (OS)	OS is defined as the time from treatment start until death from any cause.	Up to 50 months
Secondary	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
Secondary	Occurrence of treatment-emergent adverse events (AEs) during the on-treatment period		Up to 30 months
Secondary	Occurrence of treatment-emergent AEs leading to trial drug discontinuation during the on-treatment period		Up to 30 months
Secondary	Change from baseline in European Organisation for Research and Treatment (EORTC) Quality of Life Questionnaire (QLQ)-C30 physical functioning domain score	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
Secondary	Change from baseline in EORTC QLQ-C30 fatigue domain score	It is part of QLQ-C30 and uses 4-point scale (1=not at all to 4=very much)	Up to 30 months
Secondary	Change from baseline in EORTC QLQ-C30 role functioning domain score	It is part of QLQ-C30 and uses 4-point scale (1=not at all to 4=very much)	Up to 30 months
Secondary	Change from baseline in EORTC QLQ-BIL21 tiredness domain score	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

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