Journal
FUTURE ONCOLOGY
Volume -, Issue -, Pages -Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/fon-2022-1291
Keywords
BI 907828; dedifferentiated liposarcoma; doxorubicin; MDM2-p53 antagonist; phase II/III trial
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This article describes an ongoing clinical trial evaluating the efficacy of BI 907828 versus doxorubicin as first-line treatment for advanced DDLPS. The study shows that BI 907828 is able to inhibit the growth of DDLPS and has better efficacy compared to the chemotherapy drug doxorubicin.
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 theMDM2gene, 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 firstline treatment for advanced DDLPS. Plain language summary: Dedifferentiated liposarcoma (DDLPS) is a rare, fast-growing cancer that begins in fat cells. Patients with DDLPS that cannot be removed surgically or has spread to other areas of the body are usually treated with chemotherapy at first, but this typically stops working only 2-4 months after the start of treatment and has a lot of side effects. The drug BI 907828 works differently to chemotherapy by specifically targeting a gene called MDM2. This gene is abnormally increased in most DDLPS tumors and causes cancer by shutting down one of the pathways that the body uses to kill cancerous cells. BI 907828 restores this pathway, leading to the targeted destruction of tumor cells. Results from initial studies show that BI 907828 is able to slow the growth of DDLPS, and is now being investigated further, in a study called Brightline-1. Brightline-1, which is currently underway, is comparing BI 907828 with the chemotherapy drug doxorubicin for the initial treatment of DDLPS that is inoperable or has spread to other areas of the body.
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