MDM2 amplification + TP53 wild-type

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.

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.

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).

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.