Brightline-2: a phase IIa/IIb trial of brigimadlin (BI 907828) in advanced biliary tract cancer, pancreatic ductal adenocarcinoma or other solid tumors

Changhoon Yoo; Angela Lamarca; Hye Jin Choi; Arndt Vogel; Michael J Pishvaian; Lipika Goyal; Makoto Ueno; Angela Märten; Michael Teufel; Lijiang Geng; Chigusa Morizane

doi:10.2217/fon-2023-0963

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Brightline-2: a phase IIa/IIb trial of brigimadlin (BI 907828) in advanced biliary tract cancer, pancreatic ductal adenocarcinoma or other solid tumors

Authors: Changhoon Yoo ; Angela Lamarca ; Hye Jin Choi ; Arndt Vogel ; Michael J Pishvaian ; Lipika Goyal ; Makoto Ueno ; Angela Märten ; Michael Teufel ; Lijiang Geng ; Chigusa Morizane

Citation: FUTURE ONCOLOGY, Vol.20(16) : 1069-1077, 2024-01

Journal Title: FUTURE ONCOLOGY

ISSN: 1479-6694

Issue Date: 2024-01

MeSH: Biliary Tract Neoplasms* / drug therapy ; Biliary Tract Neoplasms* / pathology ; Carcinoma, Pancreatic Ductal* / drug therapy ; Carcinoma, Pancreatic Ductal* / mortality ; Carcinoma, Pancreatic Ductal* / pathology ; Female ; Humans ; Lung Neoplasms / drug therapy ; Lung Neoplasms / pathology ; Pancreatic Neoplasms* / drug therapy ; Pancreatic Neoplasms* / pathology ; Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors ; Tumor Suppressor Protein p53* / genetics ; Tumor Suppressor Protein p53* / metabolism ; Urinary Bladder Neoplasms / drug therapy ; Urinary Bladder Neoplasms / mortality ; Urinary Bladder Neoplasms / pathology

Keywords: BI 907828 ; BTC ; MDM2 ; PDAC ; Phase II trial ; TP53 ; brigimadlin ; cholangiocarcinoma ; gallbladder

Abstract: Mouse double minute 2 homolog (MDM2) is a key negative regulator of the tumor suppressor p53. Blocking the MDM2-p53 interaction, and restoring p53 function, is therefore a potential therapeutic strategy in MDM2-amplified, TP53 wild-type tumors. MDM2 is amplified in several tumor types, including biliary tract cancer (BTC), pancreatic ductal adenocarcinoma (PDAC), lung adenocarcinoma and bladder cancer, all of which have limited treatment options and poor patient outcomes. Brigimadlin (BI 907828) is a highly potent MDM2-p53 antagonist that has shown promising activity in preclinical and early-phase clinical studies. This manuscript describes the rationale and design of an ongoing phase IIa/IIb Brightline-2 trial evaluating brigimadlin as second-line treatment for patients with advanced/metastatic BTC, PDAC, lung adenocarcinoma, or bladder cancer.