Brightline-2: a phase IIa/IIb trial of brigimadlin (BI 907828) in advanced biliary tract cancer, pancreatic ductal adenocarcinoma or other solid tumors

Figures & data

Figure 1. Brigimadlin mechanism of action in MDM2-amplified, TP53 wild-type tumor cells.

MDM2: Mouse double minute 2 homolog; p53: Protein 53; wt: Wild-type.

Figure 2. Efficacy summary in patients with advanced BTC treated in two phase Ia/b trials.

BTC: Biliary tract carcinoma; DoT: Duration of treatment; PD: Progressive disease; PFS: Progression-free survival; PR: Partial response; SD: Stable disease.

Figure 3. Brightline-2 trial design.

CN: China; MDM2: Mouse double minute-2 homolog; TP53: Tumor protein 53.

Table 1. Selected inclusion and exclusion criteria.

Inclusion criteria	Exclusion criteria
Adults (≥18 years old) with advanced or metastatic, unresectable, MDM2-amplified, TP53 wild-type solid tumors: biliary tract cancer (intra- and extra-hepatic cholangiocarcinoma, gallbladder cancer and ampullary cancer), PDAC, lung adenocarcinoma, or bladder cancer (urothelial bladder cancer)	Previous administration of brigimadlin (BI 907828) or any other MDM2–p53 or MDMX (MDM4)–p53 antagonist
Written report indicating MDM2 amplification (copy number ≥8) and TP53 status, confirmed by a tissue-based test (NGS; not liquid biopsy)^† Archival tissue sample must be provided for retrospective confirmation of MDM2 amplification and TP53 status	Major surgery performed within 4 weeks prior to study treatment or planned within 6 months after screening
Receipt of appropriate prior SoC therapy unless, in the opinion of the investigator, patients are unlikely to derive clinically meaningful benefit from such treatment	Active bleeding or significant risk of hemorrhage
At least one measurable target lesion according to RECIST v1.1	Previous or concomitant malignancies that may affect treatment efficacy or trial outcome
ECOG PS status 0 or 1	Use of restricted medications likely to interfere with safe conduct of the trial
Adequate liver, bone marrow and renal function	Receiving treatment for brain metastases or leptomeningeal disease that may interfere with assessment of trial end points

† MDM2 and TP53 status are confirmed centrally, except in cases where the local test has used the same NGS provider; in China a central laboratory will perform all analyses for patients enrolled in China, applying a similar NGS platform (Cohort 1-CN).

BTC: Biliary tract carcinoma; ECOG PS: Eastern Cooperative Oncology Group performance status; NGS: Next-generation sequencing; MDM2: Mouse double minute 2; PDAC: Pancreatic ductal adenocarcinoma; RECIST v1.1: Response Evaluation Criteria in Solid Tumors, version 1.1; SoC: Standard of care; TP53: Tumor protein p53.