140TiP Brightline-4: A phase III open-label, single-arm, multicentre study to assess the safety and efficacy of brigimadlin (BI 907828), an MDM2-p53 antagonist, in patients with treatment-naïve or pretreated advanced dedifferentiated liposarcoma

Current treatment options for dedifferentiated liposarcoma (DDLPS) are associated with suboptimal efficacy and substantial toxicities. Brigimadlin (BI 907828) is a highly potent, orally available MDM2–p53 antagonist that binds to MDM2 and blocks its interaction with p53, thereby restoring p53 function, leading to cell cycle arrest and apoptosis in TP53 wild-type tumours. Brigimadlin has been evaluated in a phase Ia/Ib study in patients with solid tumours (NCT03449381) and has shown preliminary encouraging efficacy in patients with DDLPS. Based on these data, brigimadlin is being investigated for the first-line treatment of advanced DDLPS in the randomised phase II/III Brightline-1 trial (NCT05218499). The Brightline-4 trial will generate additional safety and efficacy data in a broader DDLPS patient population. Brightline-4 (NCT06058793) is an open-label, single-arm, global, multicentre phase III study that aims to assess the safety and efficacy of brigimadlin in patients with treatment-naïve or pretreated advanced DDLPS. Approximately 240 patients with treatment-naïve (Cohort A) or pre-treated (Cohort B) advanced DDLPS will be enrolled. All patients will receive brigimadlin 45 mg orally once every 3 weeks. Key inclusion criteria are: ≥18 years of age; locally advanced/metastatic, unresectable, histologically confirmed DDLPS; tumour-MDM2 expression by immunohistochemistry or MDM2 amplification (demonstrated by FISH or NGS); ≥1 measurable target lesion (RECIST v1.1); and ECOG PS 0/1. A key exclusion criterion is prior treatment with an MDM2–p53 antagonist. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoints are the occurrence of treatment-emergent adverse events (TEAEs) and grade ≥3 TEAEs according to NCI CTCAE v5. Secondary endpoints include objective response, progression-free survival, overall survival, duration of response, disease control and further assessment of safety. All analyses will be descriptive; no hypothesis testing is planned. NCT06058793. Medical writing support for the development of this abstract, under the direction of the authors, was provided by Holly Morgan, PhD, of Ashfield MedComms, an Inizio company, and funded by Boehringer Ingelheim. Boehringer Ingelheim. Boehringer Ingelheim.