Clinical trial NCT05512377: Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Pancreatic Neoplasms
Solid Tumors
Biliary Tract Cancer
Lung Neoplasms
Bladder Cancer
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2022-08-23
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective response (OR)
timeFrame: Up to 30 months
Secondary outcomes:
measure: Duration of objective response (DOR)
timeFrame: Up to 30 months
measure: Progression-free survival (PFS)
timeFrame: Up to 30 months
measure: Overall survival (OS)
timeFrame: Up to 50 months
measure: Disease control (DC)
timeFrame: Up to 30 months
measure: Occurrence of treatment-emergent adverse events (AEs) during the on-treatment period
timeFrame: Up to 30 months
measure: Occurrence of treatment-emergent AEs leading to trial drug discontinuation during the on-treatment period
timeFrame: Up to 30 months
measure: Change from baseline in European Organisation for Research and Treatment (EORTC) Quality of Life Questionnaire (QLQ)-C30 physical functioning domain score
timeFrame: Up to 30 months
measure: Change from baseline in EORTC QLQ-C30 fatigue domain score
timeFrame: Up to 30 months
measure: Change from baseline in EORTC QLQ-C30 role functioning domain score
timeFrame: Up to 30 months
measure: Change from baseline in EORTC QLQ-BIL21 tiredness domain score
timeFrame: Up to 30 months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Southern Cancer Center
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Santa Rosa
country: United States
facility: Providence Medical Foundation-Santa Rosa -69764
state: California
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers-Lone Tree-69498
state: Colorado
city: Washington
country: United States
facility: Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital
state: District of Columbia
city: Louisville
country: United States
facility: Norton Cancer Institute, Downtown
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Omaha
country: United States
facility: Nebraska Cancer Specialists-Omaha-69066
state: Nebraska
city: Mineola
country: United States
facility: Perlmutter Cancer Center at NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates of Oregon, PC
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Randwick
country: Australia
facility: Prince of Wales Hospital-Randwick-66496
state: New South Wales
city: South Brisbane
country: Australia
facility: ICON-South Brisbane-69267
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH - Barmherzige Schwestern
city: Wiener Neustadt
country: Austria
facility: LK Wiener Neustadt
city: Edegem
country: Belgium
facility: Edegem - UNIV UZ Antwerpen
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: Dijon
country: France
facility: CTR Georges-François Leclerc
city: Villejuif
country: France
facility: INS Gustave Roussy
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest, Frankfurt
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: München
country: Germany
facility: Klinikum der Universität München AÖR
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Chiba, Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Kanagawa, Yokohama
country: Japan
facility: Kanagawa Cancer Center
city: Miyagi, Sendai
country: Japan
facility: Tohoku University Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokyo, Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Tokyo, Koto-ku
country: Japan
facility: Japanese Foundation for Cancer Research
city: Yamaguchi, Ube
country: Japan
facility: Yamaguchi University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Riyadh
country: Saudi Arabia
facility: King Abdul Aziz Medical City
city: Singapore
country: Singapore
facility: National University Hospital-Singapore-42005
city: KwaZulu
country: South Africa
facility: Rainbow Oncology
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Bern
country: Switzerland
facility: University Hospital Bern/Inselspital Bern
city: Genève 14
country: Switzerland
facility: University Hospital Geneva
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Cancer Center
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital
city: Muang
country: Thailand
facility: Srinagarind Hospital
city: London
country: United Kingdom
facility: University College Hospital
Study officials:
References: