First patient dosed in the first-in-human study of a novel ATR inhibitor

January 10, 2021 (Shanghai, China) – Jiangsu Hengrui Pharmaceuticals Co., Ltd. announced that the first patient has been dosed in a First-In-Human (FIH) Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics (PK) of a novel ataxia telangiectasia and rad3 related protein (ATR) inhibitor in patients with advanced malignant tumors.

About the Novel ATR Inhibitor

Hengrui’s orally administered novel ATR inhibitor showed promising preclinical efficacy and safety profile. Under the same dosage, this novel ATR inhibitor exhibited stronger anti-tumor efficacy as monotherapy in various animal tumor models versus a positive control which is a potent ATR inhibitor that, based on a published paper, demonstrated superior in vivo anti-tumor efficacy as monotherapy when compared with several other ATR inhibitors in clinical development.1 In addition to the demonstrated therapeutic effect as monotherapy, strongly enhanced anti-tumor effect was observed of Hengrui’s ATR inhibitor in combination with fuzuloparib, a marketed PARP inhibitor developed by Hengrui, in a triple negative breast cancer xenograft model.  

About the Study

This FIH trial (NCT05144061) is a single-arm, open-label, dose-escalation study of the orally administered ATR inhibitor in subjects with advanced malignant tumor, which is planned to enroll 116 patients.

The primary endpoint is to determine the dose-limiting toxicities, the maximum tolerated dose, and the recommended Phase 2 dose of this ATR inhibitor. The secondary endpoints include PK, number and severity of adverse events, and preliminary efficacy profile of the drug candidate in patients with advanced malignant tumor.

About ATR

ATR is a key kinase at the heart of the DNA damage response (DDR) machinery, responsible for sensing replication stress (RS) and signaling it to S and G2/M checkpoints to facilitate repair.2 Inhibiting the DDR is an attractive therapeutic concept in cancer therapy, since (i) resistance to genotoxic therapies has been associated with increased DDR signaling, and (ii) many cancers have defects in certain components of the DDR rendering them highly dependent on the remaining DDR pathways for survival.3 Supported by strong preclinical evidence, in addition to being developed as monotherapy, multiple ATR inhibitors are currently under clinical development in combination with chemotherapy, radiotherapy, PARP inhibitors, and immune checkpoint inhibitors for advanced malignant tumors. 2,4

About Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Hengrui is a leading global pharmaceutical company headquartered in China with a focus on research, development, manufacturing, and commercialization of innovative and high-quality healthcare products. Innovation is the core development strategy. Hengrui ranked the 24th among the top 1,000 global pharma companies in 2021.5 Hengrui has been on the Pharma Exec’s annual listing of the top global pharmaceutical companies for the third consecutive year, rising from the 47th in 2019 to the 38th in 2021.

1. Wengner, A. M. et al. The Novel ATR Inhibitor BAY 1895344 Is Efficacious as Monotherapy and Combined with DNA Damage-Inducing or Repair-Compromising Therapies in Preclinical Cancer Models. Molecular Cancer Therapeutics, 19(1), 26–38 (2020).

2. Bradbury, A. et al. Targeting ATR as Cancer Therapy: A new era for synthetic lethality and synergistic combinations? Pharmacology & Therapeutics, 207, 107450 (2020).

3. Weber, A. M. et al. ATM and ATR as therapeutic targets in cancer. Pharmacology & Therapeutics, 149, 124–138 (2015).

4. Barnieh, F. M. et al. Progress towards a clinically-successful ATR inhibitor for cancer therapy. Current Research in Pharmacology and Drug Discovery, 2, 100017 (2021).


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