A Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the ATR Kinase Inhibitor ART0380 Administered Orally as Monotherapy and in Combination to Patients with Advanced or Metastatic Solid Tumors

ART0380 selectively targets and inhibits ATR activity and blocks the downstream phosphorylation of the serine/threonine protein kinase checkpoint kinase 1 (CHK1). This prevents ATR-mediated signaling, which 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 alone or in combination with Irinotecan with an acceptable level of side effects
• The effects of the study drug alone or in combination with Irinotecan (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
• If research tests can be used in the future to predict who will benefit from the study drug

There are two parts to this study in which ART0380 will be given to subjects either on its own or in combination with irinotecan.

The study will be divided into ‘cycles’ of 21 days each. You will receive ART0380 on an intermittent schedule in combination with a standard dose of irinotecan.

The Study Drug should be swallowed whole and taken at about the same time each day.

Irinotecan will be given to subjects intravenously (in the vein [IV] by injection) at the study site over a period of 90 minutes on Day 1 and Day 8 of each cycle.