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    BIOMARKER:

    MDM2 amplification + TP53 wild-type

    i
    Other names: MDM2, HDM2, MGC5370, MDM2 proto-oncogene, E3 ubiquitin protein ligase, TP53, Tumor Protein P53, Cellular Tumor Antigen P53, Phosphoprotein P53, Tumor Protein P53, Antigen NY-CO-13, Transformation-Related Protein 53, Mutant Tumor Protein 53, P53 Tumor Suppressor, Tumor Suppressor P53, Tumor Protein 53, BMFS5, TRP53, BCC7, LFS1
    Entrez ID:
    7157; 4193
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    2ms
    Discovery and Characterization of Brigimadlin, a Novel and Highly Potent MDM2-p53 Antagonist Suitable for Intermittent Dose Schedules. (PubMed, Mol Cancer Ther)
    Exploratory clinical pharmacokinetic studies (NCT03449381) showed high systemic exposure and a long plasma elimination half-life in cancer patients who received oral brigimadlin. These findings support the continued clinical evaluation of brigimadlin in patients with MDM2-amplified cancers, such as dedifferentiated liposarcoma.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase)
    |
    TP53 mutation • TP53 wild-type • MDM2 amplification + TP53 wild-type
    |
    brigimadlin (BI 907828)
    11ms
    Brightline-2: a phase IIa/IIb trial of brigimadlin (BI 907828) in advanced biliary tract cancer, pancreatic ductal adenocarcinoma or other solid tumors. (PubMed, Future Oncol)
    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.
    P2a data • Review • Journal • Metastases
    |
    TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)
    |
    TP53 wild-type • MDM2 amplification + TP53 wild-type • TP53 amplification
    |
    brigimadlin (BI 907828)
    over1year
    A phase I dose-escalation and expansion study evaluating the safety and efficacy of the MDM2–p53 antagonist brigimadlin (BI 907828) in patients (pts) with solid tumours (ESMO 2023)
    Conclusions BI 907828 demonstrated antitumour activity and a manageable safety profile in pts with advanced solid tumours, including those with BTC; dose expansion is ongoing. BI 907828 is being further assessed in pts with BTC in the phase IIa/IIb open-label Brightline-2 trial (NCT05512377).
    Clinical • P1 data
    |
    MDM2 (E3 ubiquitin protein ligase)
    |
    TP53 wild-type • MDM2 amplification + TP53 wild-type
    |
    brigimadlin (BI 907828)
    over1year
    Brightline-2: A phase IIa/IIb, open-label trial of the MDM2–p53 antagonist BI 907828 in patients with advanced MDM2-amplified, TP53 wild-type biliary tract cancer, pancreatic ductal adenocarcinoma, or other selected solid tumours (ESMO-GI 2023)
    Currently, ten patients with BTC had received BI 907828 ± ezabenlimab (an immune checkpoint inhibitor). The final primary analysis will be performed after all treated patients have been followed for ≥12 weeks, or until study discontinuation. As of February 2023, 16 patients have been enrolled.Clinical trial identification: NCT05512377.Editorial acknowledgement: Medical writing assistance, funded by Boehringer Ingelheim, was provided by Jim Sinclair, PhD, of Ashfield MedComms, an Inizio Company, during the preparation of this abstract.Legal entity responsible for the study: Boehringer Ingelheim.
    Clinical • P2a data • Metastases
    |
    TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)
    |
    TP53 wild-type • MDM2 amplification • MDM2 amplification + TP53 wild-type • TP53 amplification
    |
    brigimadlin (BI 907828) • ezabenlimab (BI 754091)