Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Yap, TA; Tan, DSP; Terbuch, A; Caldwell, R; Guo, C; Goh, BC; Heong, V; Haris, NRM; Bashir, S; Drew, Y; Hong, DS; Meric-Bernstam, F; Wilkinson, G; Hreiki, J; Wengner, AM; Bladt, F; Schlicker, A; Ludwig, M; Zhou, Y; Liu, L; Bordia, S; Plummer, R; Lagkadinou, E; de Bono, JS.
First-in-Human Trial of the Oral Ataxia Telangiectasia and RAD3-Related (ATR) Inhibitor BAY 1895344 in Patients with Advanced Solid Tumors.
Cancer Discov. 2021; 11(1):80-91 Doi: 10.1158/2159-8290.CD-20-0868 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Co-Autor*innen der Med Uni Graz
Terbuch Angelika

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Targeting the ataxia telangiectasia and RAD3-related (ATR) enzyme represents a promising anticancer strategy for tumors with DNA damage response (DDR) defects and replication stress, including inactivation of ataxia telangiectasia mutated (ATM) signaling. We report the dose-escalation portion of the phase I first-in-human trial of oral ATR inhibitor BAY 1895344 intermittently dosed 5 to 80 mg twice daily in 21 patients with advanced solid tumors. The MTD was 40 mg twice daily 3 days on/4 days off. Most common adverse events were manageable and reversible hematologic toxicities. Partial responses were achieved in 4 patients and stable disease in 8 patients. Median duration of response was 315.5 days. Responders had ATM protein loss and/or deleterious ATM mutations and received doses ≥40 mg twice daily. Overall, BAY 1895344 is well tolerated, with antitumor activity against cancers with certain DDR defects, including ATM loss. An expansion phase continues in patients with DDR deficiency. SIGNIFICANCE: Oral BAY 1895344 was tolerable, with antitumor activity in heavily pretreated patients with various advanced solid tumors, particularly those with ATM deleterious mutations and/or loss of ATM protein; pharmacodynamic results supported a mechanism of action of increased DNA damage. Further study is warranted in this patient population.See related commentary by Italiano, p. 14.This article is highlighted in the In This Issue feature, p. 1. ©2020 American Association for Cancer Research.

© Med Uni Graz Impressum