Reference Detail

Ref Type

Abstract

PMID

Authors

P. Schoeffski N. Yamamoto T. Bauer M. Patel M.M. Gounder J. Geng R. Sailer G. Jayadeva P. Lorusso

Title

A phase I dose-escalation and expansion study evaluating the safety and efficacy of the MDM2–p53 antagonist BI 907828 in patients (pts) with solid tumours

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	33	Supplement 7	Sep 1, 2022

URL

https://www.annalsofoncology.org/article/S0923-7534(22)02432-2/fulltext

Abstract Text

Background BI 907828, a highly potent mouse double minute-2 (MDM2)–p53 antagonist, has demonstrated preclinical antitumour activity, particularly in TP53 wild-type (wt), MDM2-amplified dedifferentiated liposarcoma (DDLPS) models. This phase I study is evaluating BI 907828 in pts with advanced solid tumours. During dose-escalation (phase Ia), the selected recommended dose for expansion (RDE) was 45 mg q3w (Gounder M, 2021). Methods During dose-expansion (phase Ib), pts were enrolled to Cohort 1 (TP53wt, MDM2-amplified sarcoma) or Cohort 2 (other TP53wt, MDM2-amplified solid tumours). Pts in Cohort 1 received BI 907828 45 mg q3w; pts in Cohort 2 received 30 or 40 mg on Days 1 and 3 of a 28-day cycle, with a safety run-in of the initial 6 pts per dose level, or 45 mg q3w (biliary tract cancer pts only). The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response and the number of pts with grade ≥3 treatment-related adverse events (AEs). Results As of March 2022, 94 pts were enrolled; 50 (53.2%) were male, 57/36 (60.6%/38.3%) had ECOG PS 0/1, respectively; the median number of prior systemic therapies was 2 (range: 0–11). At data cut off, 45/48 pts with advanced LPS were evaluable for tumour response. Disease control rate (complete + partial response (PR) + stable disease) was 93%/88% in pts with DDLPS/well-differentiated LPS (WDLPS), respectively. A confirmed PR was achieved in 5 pts (2 DDLPS, 3 WDLPS); 3 pts (2 DDLPS, 1 WDLPS) had an unconfirmed PR. Of the pts enrolled into phase Ia, 5/11 with DDLPS and 4/8 with WDLPS achieved a PFS >10.5 months. For pts with other solid tumours, 2/4 with MDM2-amplified biliary tract cancer and 1 with MDM2-amplified pancreatic adenocarcinoma had a confirmed PR. Of the 46 pts who received the RDE, 22 (47.8%) had grade ≥3 AEs; the most common were neutropenia (21.8%) and thrombocytopenia (19.6%). Serious AEs were experienced by 9 pts; the most common were nausea (n=3), pyrexia, abdominal pain, and thrombocytopenia (n=2 each). Conclusions BI 907828 demonstrated antitumour activity and a manageable safety profile in pts with advanced solid tumours, including LPS. The dose-expansion phase is ongoing.

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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