The ATR inhibitor ceralasertib potentiates cancer checkpoint immunotherapy by regulating the tumor microenvironment.

The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer patients who progressed on immunotherapy. Here we show that modelling of intermittent ceralasertib treatment in mouse tumor models reveals CD8 T-cell dependent antitumor activity, which is separate from the effects on tumor cells. Ceralasertib suppresses proliferating CD8 T-cells on treatment which is rapidly reversed off-treatment.

Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced gastric cancer.

Background: Targeting the DNA damage repair (DDR) pathways is an attractive strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral kinase inhibitor of ataxia telangiectasia and Rad3 related protein, which is a master regulator of DDR. We conducted a phase II trial of ceralasertib plus durvalumab in patients with previously treated advanced gastric cancer (AGC) to demonstrate the safety, tolerability, and clinical activity of the combination.

Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced/metastatic melanoma who have failed prior anti-PD-1 therapy.

Background: Modulating the DNA damage response and repair (DDR) pathways is a promising strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related protein, which is crucial for DDR.

Patients And Methods: This phase II trial evaluated ceralasertib plus durvalumab for the treatment of patients with metastatic melanoma who had failed anti-programmed cell death protein 1 therapy.

Phase I Study of Ceralasertib (AZD6738), a Novel DNA Damage Repair Agent, in Combination with Weekly Paclitaxel in Refractory Cancer.

Purpose: Ceralasertib is a potent and selective oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related (ATR) protein.

Patients And Methods: Eligible patients with solid tumors, enriched for melanoma, received ceralasertib in combination with a fixed dose of paclitaxel (80 mg/m on D1, D8, D15) in 28-day cycles. The dose of ceralasertib was escalated to reach an MTD in a rolling 6 design.

A Phase I/Randomized Phase II Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Nintedanib versus Sorafenib in Asian Patients with Advanced Hepatocellular Carcinoma.

Background: Nintedanib is an oral, triple angiokinase inhibitor of vascular endothelial growth factor/platelet-derived growth factor/fibroblast growth factor receptors. This randomized, multicenter, open-label, phase I/II study evaluated the safety, pharmacokinetics, maximum tolerated dose (MTD) in terms of dose-limiting toxicities (DLTs), and efficacy of nintedanib versus sorafenib in Asian patients with unresectable advanced hepatocellular carcinoma (HCC).

Patients And Methods: For the phase I portion, patients were stratified into two groups according to their alanine aminotransferase/aspartate aminotransferase (ALT/AST) and Child-Pugh score at baseline.