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

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 Jan 12. doi: 10.2217/fon-2023-0963.
Changhoon Yoo 1,  Angela Lamarca 2,  Hye Jin Choi 3,  Arndt Vogel 4 5,  Michael J Pishvaian 6,  Lipika Goyal 7,  Makoto Ueno 8,  Angela Märten 9,  Michael Teufel 10,  Lijiang Geng 11,  Chigusa Morizane 12
Affiliations

Affiliations

  • 1 Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
  • 2 Department of Medical Oncology, Fundacion Jimenez Diaz University Hospital, 28040 Madrid, Spain.
  • 3 Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
  • 4 Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, 0625 Hannover, Germany.
  • 5 Department of Gastroenterology & Hepatology, Toronto General Hospital, Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, M5G 2C4, Canada.
  • 6 Department of Oncology, John Hopkins University, Washington, DC 20016, USA.
  • 7 Stanford Cancer Center, Palo Alto, CA 94305, USA.
  • 8 Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan.
  • 9 Boehringer Ingelheim International GmbH, 55218 Ingelheim am Rhein, Germany.
  • 10 Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT 0687, USA.
  • 11 Boehringer Ingelheim (China) Investment Co., Shanghai 200040, China.
  • 12 Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
PMID: 38214149 DOI: 10.2217/fon-2023-0963
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.

Keywords

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

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