Brightline-1: phase II/III trial of the MDM2-p53 antagonist BI 907828 versus doxorubicin in patients with advanced DDLPS.
Patrick SchöffskiMehdi LahmarAnthony LucarelliRobert G MakiPublished in: Future oncology (London, England) (2023)
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.
Keyphrases
- phase ii
- poor prognosis
- open label
- clinical trial
- double blind
- phase iii
- placebo controlled
- long non coding rna
- squamous cell carcinoma
- drug delivery
- cancer therapy
- small cell lung cancer
- gene expression
- locally advanced
- radiation therapy
- mesenchymal stem cells
- stem cells
- dna methylation
- cell therapy
- binding protein
- drug induced
- nucleic acid
- case control