A Phase 1/2a, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Trial of Oral ATRN-119 in Patients with Advanced Solid Tumors

• ATRN-119 selectively targets and binds to ATR, and inhibits its activity and ATR-mediated signaling. This blocks the downstream phosphorylation of the serine/threonine protein kinase checkpoint kinase 1 (CHK1). This results in the inhibition of DNA damage checkpoint activation, the disruption of DNA damage repair, and the induction of tumor cell apoptosis.

In this study, the sponsor and investigators want to learn:

• How much of the study drug can be given with an acceptable level of side effects
• The effects of the study drug (good and bad)
• How much of the study drug is absorbed into the blood and how fast it is removed
• How the study drug is acting on your body

This study has 2 parts, dose escalation and dose expansion.

Dose Escalation means that the amount of the study agent given will be increased in each group of research participants, to find the most appropriate dose for further study.

In the Dose Expansion part of the study, a larger number of people receive the study agent dose determined to be appropriate in the dose escalation part of the study.

During the study, you will take the study agent starting with the first cycle. Each cycle is 28 days. On clinic days, you will be dosed with ATRN-119 once daily in the morning at least 1 hour prior to a meal. The dose assigned may be increased as the cohort proceeds. In Part 1, the study doctors will tell you about visit days where you will either fast or eat a full meal before taking ATRN-119. This is done so that researchers can study the effect of food on ATRN-119.   There may be additional cycles if you are responding to the study agent and tolerating it.

You will be given a supply of the study agent to take at home and you will also be given a diary to record details of all of your doses. You will need to bring both your study agent supply (even empty bottles) and diary with you to every visit. Also, please note that on visit days, you will not take your dose at home; instead, your dose will be given to you during your visit, at the direction of the study staff.