First In Human Trial Of The Oral Ataxia Telangiectasia and RAD 3 Related (ATR) Inhibitor BAY 1895344 In Patients With Advanced Solid Tumors

There has long been speculation that the ataxia telangiectasia and RAD 3 related (ATR) enzyme is a promising target for cancer therapeutics.  In particular, for patients that have underlying DNA damage response (DDR) defects with replication stress and activation of the ataxia telangiectasia mutated signaling pathway.  

The investigators report the dose escalation component of a phase 1 first in human clinical trial of the oral ATR inhibitor BAY 1895344 that was intermittently dosed between 5 to 80 mg twice daily.  Treatment occurred in 21 patients with a variety of advanced solid tumors.  The maximum tolerated dose was 40 mg twice daily 3 days on and 4 days off.  Adverse events were reported as manageable.  Hematologic toxicities were noted to be reversible. 

Partial responses were achieved in 4 patients and stable disease was seen in 8 patients.  The median duration of response was reported as 315 days.  ATM protein loss and/or deleterious ATM mutations were noted in patients who were responders.  Responders received at least 40 mg twice daily of the oral agent.  

The authors concluded ” 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”