Brightline-1: phase II/III trial of the MDM2–p53 antagonist BI 907828 versus doxorubicin in patients with advanced DDLPS

Figures & data

Infographic: A PDF version of this infographic is available as supplemental material.

Figure 1. Mechanism of action of BI 907828.

wt: Wild-type.

Figure 2. Brightline-1 trial design.

Patients may continue treatment with doxorubicin for up to six cycles (maximum cumulative dose of 450 mg/m²); patients randomized to the doxorubicin arm will be eligible to cross-over to receive BI 907828 following confirmed progressive disease and if eligibility criteria are met.

IV: Intravenous; PD: Pharmacodynamic; PFS: Progression-free survival; PK: Pharmacokinetic; Q3W: Every 3 weeks.

Table 1. Key inclusion and exclusion criteria.

Inclusion criteria	Exclusion criteria
Confirmed, advanced/metastatic, unresectable, progressive/recurrent DDLPS^†	Known mutation in the TP53 gene (screening for TP53 status is not required)
Adult patients (≥18 years old)	Major surgery performed within 4 weeks prior to randomization or planned within 6 months after screening
Positive MDM2 immunohistochemistry as demonstrated by fluorescence in situ hybridization or MDM2 amplification demonstrated by next generation sequencing	Prior systemic therapy for LPS or prior treatment with anthracyclines in any setting
At least one measurable target lesion according to RECIST v1.1	Previous or concomitant malignancies other than DDLPS or WDLPS, treated within 5 years
ECOG PS 0 or 1	History/presence of human immunodeficiency virus infection, hepatitis B or C virus infection, gastrointestinal disorders, cardiovascular abnormalities or brain metastases
Adequate liver, bone marrow and renal function

† Advanced refers to locally advanced or metastatic disease, and locally advanced refers to unresectable (surgery morbidity would outweigh potential benefits). Per the trial protocol, locally advanced DDLPS is defined as DDLPS without metastatic spread via the blood vessels or the lymphatic system. For this trial, metastatic DDLPS is defined as DDLPS with metastatic spread via the blood vessels or the lymphatic system. Patients with grade 1 or grade 2 DDLPS can be eligible; however, advanced/metastatic grade 1 or 2 DDLPS is not common so the focus is on patients with advanced/metastatic disease.

DDLPS: Dedifferentiated liposarcoma; ECOG PS: Eastern Cooperative Oncology Group performance status; LPS: Liposarcoma; RECIST v1.1: Response Evaluation Criteria In Solid Tumors version 1.1; WDLPS: Well-differentiated liposarcoma.