The first patient has been dosed in a phase 1 trial evaluating a monotherapy treatment in people with advanced solid tumors and hematologic malignancies in Australia.
Safety and tolerability of ATG-018
The primary objective of the study is to evaluate the safety and tolerability of the drug and to determine the maximum tolerated dose and/or recommended phase 2 dose (RP2D) and the biologically effective dose and preliminary efficacy if available.
The secondary objective is to characterize the pharmacology of ATG-018.
The drug is an orally-available, potent, selective small molecule ATR (ataxia telangiectasia and Rad3-related) inhibitor. ATG-018 inhibits the ATR kinase, which limits cancer cells’ ability to repair damaged DNA, in a mechanism also known as synthetic lethality or the DDR.
Jim Coward, professor at the University of Queensland School of Medicine, said: “In human cells, a variety of repair mechanisms exist to maintain genomic integrity, and defects in these pathways cause genome instability and promote tumorigenesis.
“Many cancer cells have high level replication stress and rely on their S/G2 checkpoints for survival following DNA damage. This renders tumor cells more susceptible to inhibition of ATR and targeting this may be a novel therapeutic strategy.
“ATG-018, is an oral, potent, and selective inhibitor of ATR. Preclinical studies have demonstrated potent activity against ATR in enzyme inhibition assays and tumor cell lines including both solid tumors and hematological malignancies. We are encouraged by these findings, and eager to further evaluate the therapeutic potential of ATG-018 for patients.”
Jay Mei, Antengene’s founder, chairman and CEO said: “ ATG-018 is a novel in-house discovered and developed drug candidate to enter the clinical stage. I am very proud of the joint efforts from the teams at Antengene and the clinical organizations to bring this compound to the clinical stage.”
He said that data on ATG-018 presented at the 2022 American Association for Cancer Research annual meeting showed that ATG-018 demonstrates promising single-agent activity in a robust preclinical program that includes a wide range of tumor types that rely on DDR and have a need for new treatments.
He added: “In addition, early work to identify a set of predictive biomarkers could enable ATG-018 to be used as a precisionmedicine. We will work closely with our investigators to advance this clinical program and strive to develop a new treatment option for patients around the world.”