PATRIOT: A phase I study to assess the tolerability, safety and biological effects of a specific ataxia telangiectasia and Rad3-related (ATR) inhibitor (AZD6738) as a single agent and in combination with palliative radiation therapy in patients with solid tumours.

TPS2603Background: Tumour control rates from radiation therapy (RT) are limited by normal tissue toxicities. Novel strategies are required to selectively sensitize tumour cells to radiation-induced DNA damage. The G2 cell cycle checkpoint is an attractive target for this, as normal cells will be protected by their intact G1 checkpoint, which is lost in the majority of cancer cells. ATR is an important mediator of the G2 checkpoint. Preclinical data suggest that ATR inhibition will sensitise to DNA damaging therapies, including RT. This multi-part phase 1 trial aims to assess safety and tolerability and preliminary anti-tumour activity of the ATR inhibitor AZD6738 as monotherapy and in combination with palliative RT, escalating both drug and radiation dose at a dose-fractionation relevant to radical treatment. The design aims to test a novel agent at the earliest stage of clinical development and assess safety in combination with RT, with the aim of moving to a radically-treated population if tolerated. Me...