Abstract CT288: Brightline-4: A phase 3 open-label, single-arm, multicenter study to assess the safety and efficacy of brigimadlin (BI 907828) treatment in patients with treatment-naïve or pretreated advanced dedifferentiated liposarcoma

Abstract

Abstract Background Current treatment options for dedifferentiated liposarcoma (DDLPS) are associated with suboptimal efficacy and substantial toxicities. Purpose 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 tumors. Brigimadlin has been evaluated in a phase 1a/1b study in patients with solid tumors (NCT03449381) and has shown encouraging preliminary efficacy in patients with DDLPS. Based on these data, brigimadlin is being investigated for the first-line treatment of advanced DDLPS in the randomized phase 2/3 Brightline-1 trial (NCT05218499). The Brightline-4 trial will generate additional safety and efficacy data in a broader DDLPS patient population. Experimental design Brightline-4 (NCT06058793) is an open-label, single-arm, global, multicenter phase 3 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 include: ≥18 years of age; locally advanced/metastatic, unresectable, histologically confirmed DDLPS; tumor MDM2 expression by immunohistochemistry or MDM2 amplification (via fluorescence in situ hybridization or next-generation sequencing); ≥1 measurable target lesion (RECIST v1.1); and ECOG PS 0/1. Key exclusion criteria include: prior treatment with an MDM2-p53 antagonist; known mutation in TP53; receiving treatment for brain metastases or leptomeningeal disease. 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. Citation Format: Scott Schuetze, Girish Jayadeva, Michael Santoro. Brightline-4: A phase 3 open-label, single-arm, multicenter study to assess the safety and efficacy of brigimadlin (BI 907828) treatment in patients with treatment-naïve or pretreated advanced dedifferentiated liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT288.