Reference Detail

Ref Type

PMID

(38567193)

Authors

Yamamoto N, Tolcher A, Hafez N, Lugowska I, Ramlau R, Macarulla T, Geng J, Li J, Teufel M, Märten A, LoRusso P

Title

Efficacy and Safety of the MDM2-p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced Biliary Tract Cancer: A Case Series.

Journal	Vol	Issue	Date	Pages	Journal Short Title
OncoTargets and therapy	17		2024	267-280	Onco Targets Ther

URL

Abstract Text

In patients with advanced biliary tract cancer (BTC), first-line chemotherapy plus immunotherapy has improved outcomes; however, second-line options that reflect the disease's molecular heterogeneity are still needed. One emerging target is MDM2, amplified in ~5-8% of BTC cases.This is a subset analysis of two ongoing Phase Ia/Ib trials assessing patients treated with brigimadlin (BI 907828; a highly potent, oral MDM2-p53 antagonist) ± ezabenlimab (PD-1 inhibitor) ± BI 754111 (anti-LAG-3; n = 1).Results from 12 patients with BTC are shown (monotherapy: n = 6/combination: n = 6). Six patients achieved partial response (monotherapy: n = 2/combination: n = 4), four had stable disease; responses were durable. Brigimadlin had a manageable safety profile. Seven patients had dose reductions due to adverse events, but no treatment-related adverse events led to treatment discontinuation.Brigimadlin demonstrated anti-tumor activity in patients with advanced MDM2-amplified BTC, and warrants further investigation.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
MDM2 amp TP53 wild-type	intrahepatic cholangiocarcinoma	predicted - sensitive	BI 907828 + Ezabenlimab	Case Reports/Case Series	Actionable	In a Phase Ia/Ib trial, treatment with the combination of BI 907828 and Ezabenlimab (BI 754091) resulted in 3 partial responses and 1 stable disease in 4 patients with MDM2-amplified, TP53 wild-type metastatic intrahepatic cholangiocarcinoma (PMID: 38567193; NCT03964233).	38567193
MDM2 amp TP53 wild-type	intrahepatic cholangiocarcinoma	predicted - sensitive	BI 907828	Case Reports/Case Series	Actionable	In a Phase Ia/Ib trial, BI 907828 treatment resulted in a partial response in a patient with MDM2-amplified (CN=9), TP53 wild-type metastatic intrahepatic cholangiocarcinoma, with treatment lasting 12 months (PMID: 38567193; NCT03449381).	38567193
MDM2 amp TP53 wild-type	gallbladder adenocarcinoma	predicted - sensitive	BI 907828 + Ezabenlimab	Case Reports/Case Series	Actionable	In a Phase Ia/Ib trial, treatment with the combination of BI 907828 and Ezabenlimab (BI 754091) resulted in a partial response with a progression-free survival of 7.9 months in a patient with MDM2-amplified (CN=14), TP53 wild-type metastatic gallbladder adenocarcinoma (PMID: 38567193; NCT03964233).	38567193
MDM2 amp TP53 wild-type	ampulla of Vater adenocarcinoma	predicted - sensitive	BI 907828	Case Reports/Case Series	Actionable	In a Phase Ia/Ib trial, BI 907828 treatment resulted in a partial response in a patient with MDM2-amplified (CN=15) metastatic ampullary adenocarcinoma, with treatment ongoing at 19.1 months (PMID: 38567193; NCT03449381).	38567193