去分化的脂肪肉瘤（DDLPS）是一种罕见且侵袭性强、预后不佳的脂肪肉瘤。晚期/转移性DDLPS的一线治疗是系统化疗，但疗效不佳，副作用较大。大多数DDLPS肿瘤都有MDM2基因扩增，该基因编码p53抑制蛋白的负性调节因子。BI 907828是一种高效、口服的MDM2-p53拮抗剂，可抑制p53和MDM2之间的相互作用，从而恢复p53的活性。BI 907828在临床前研究和Ia/Ib期病人实验中表现出有希望的活性，尤其是在DDLPS患者中。本文描述了正在进行的Brightline-1（NCT05218499）多中心、随机、II/III期试验的基本原理和设计，该试验评估BI 907828与多柔比星作为晚期DDLPS的一线治疗。

Dedifferentiated liposarcoma (DDLPS) is a rare, aggressive liposarcoma associated with poor prognosis. First-line treatment for advanced/metastatic DDLPS is systemic chemotherapy, but efficacy is poor and toxicities substantial. Most DDLPS tumors have amplification of the MDM2 gene, which encodes a negative regulator of the p53 suppressor protein. BI 907828 is a highly potent, oral MDM2-p53 antagonist that inhibits the interaction between p53 and MDM2, thereby restoring p53 activity. BI 907828 has shown promising activity in preclinical studies and in a phase Ia/Ib study in patients with solid tumors, particularly those with DDLPS. This manuscript describes the rationale and design of an ongoing multicenter, randomized, phase II/III trial (Brightline-1; NCT05218499) evaluating BI 907828 versus doxorubicin as first-line treatment for advanced DDLPS.