Ceralasertib, an ATR Kinase Inhibitor, as Monotherapy in Japanese Patients with Advanced Solid Malignancies - Results from a Phase 1 Study

Sep 28, 2026

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Ceralasertib is an oral, selective, potent ATR serine/threonine kinase inhibitor central to cell-cycle checkpoint control and DNA damage response. The study reports preliminary safety, tolerability, and pharmacokinetic findings for ceralasertib monotherapy in Japanese patients with advanced solid tumors. In a phase 1 open-label design, patients received defined twice-daily regimens across a 28-day cycle, with safety as the primary endpoint and antitumor activity and pharmacokinetics as secondary measures, plus exploratory biomarker analyses.

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CategoryHealthcare

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Investigational New Drugs (2025) 43:1235–1246 [https://doi.org/10.1007/s10637-025-01592-x](https://doi.org/10.1007/s10637-025-01592-x) Ceralasertib, an ATR kinase inhibitor, as monotherapy in Japanese patients with advanced solid malignancies: Results from a phase 1 study Yasutoshi Kuboki1 · Nobuaki Matsubara1 · Hiromichi Nakajima1 · Takao Fujisawa1 · Takafumi Koyama2 · Jun Sato2 · Yuki Katsuya2 · Aleksandra Kmieciak3 · Daniel Slade3 · Kiyomi Iwata4 · Yusuke Takahashi4 · Masahiro Nii4 · Kosho Murayama4 · Toshio Kawata4 · Hisashi Kawasumi4 · Noboru Yamamoto2 Received: 5 August 2025 / Accepted: 17 November 2025 / Published online: 6 December 2025 © The Author(s) 2025 Abstract Background Ceralasertib is an oral, selective, and potent inhibitor of ATR serine/threonine kinase, a key protein involved in cell cycle checkpoint regulation and DNA damage response. We report preliminary safety, tolerability, and pharmacokinetic data of ceralasertib monotherapy in Japanese patients with advanced solid tumors. Methods In this phase 1, open-label study, patients orally received ceralasertib twice daily 240 mg on days 1–7 (Cohort 1) or 160 mg on days 1–14 (Cohort 2) of a 28-day cycle, respectively; both cohorts also received a single ceralasertib dose 4 days before Cycle 1. Patients were aged ≥ 18 years with solid malignancies refractory to standard therapies or for which no standard therapy exists. The primary objective was to determine ceralasertib safety; secondary objectives included assessing antitumor activity and pharmacokinetics. Exploratory objectives included biomarker analysis. Results Twelve of 14 patients screened received ceralasertib. At data cutoff (August 17, 2023), all 12 patients had experienced at least one treatment-emergent adverse event (AE; grade ≥ 3, n = 3). One patient in each cohort had a dose-limiting toxicity; no AE-related deaths were reported. In total, 6 patients had a best objective response of stable disease (Cohort 1, n = 2; Cohort 2, n = 4) . A trend suggesting dose-proportional increases in exposure following single and multiple administration of ceralasertib was observed. Conclusion Ceralasertib monotherapy was generally well tolerated in Japanese patients with advanced solid tumors. The small number of patients enrolled prevents definitive conclusions on the efficacy of ceralasertib monotherapy to be made. Trial registration [ClinicalTrials.gov](ClinicalTrials.gov), NCT05469919. Registration date: May 18, 2022. Keywords Ceralasertib · Solid tumors · ATR inhibitor · DNA damage response genes Introduction In 2022, approximately one million new cancer cases and 420,000 cancer-related deaths occurred in Japan; the three most common cancers were lung, colon, and gastric, together * Yasutoshi Kuboki [ykuboki@east.ncc.go.jp](ykuboki@east.ncc.go.jp) 1 National Cancer Center Hospital East, Chiba, Japan 2 National Cancer Center Hospital, Tokyo, Japan 3 AstraZeneca, Cambridge, UK 4 AstraZeneca K.K, Osaka, Japan accounting for approximately 40% of all new cases and over 40% of all deaths [1, 2] . Anti-programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1) antibodies have revolutionized cancer treatment, and they are now standard of care for several cancers including lung, skin, and breast [3 , 4] . However, resistance to anti-PD-(L)1 therapies is common and occurs through multiple mechanisms intrinsic or extrinsic to the tumor, including T-cell exhaustion and immunosuppression within the tumor microenvironment (TME) [5, 6] . Survival of patients who progress on antiPD-(L)1 therapies remains low, with 2-year survival rates around 15% for patients with metastatic non-small-cell lung cancer in a real-world setting [7] . With low survival rates and potential for evolving resistance to anti-PD-(L)1 therapies, new therapeutic options are needed. Ceralasertib is an oral, selective, and potent inhibitor of ATR serine/threonine kinase, a key protein involv

FAQs

What is ceralasertib and what biological role does it target?

Ceralasertib is an oral, selective inhibitor of ATR serine/threonine kinase. It modulates cell-cycle checkpoint regulation and the cellular response to DNA damage and replication stress.

How was ceralasertib administered in this phase 1 study?

Patients received ceralasertib orally twice daily, using two cohorts with different dose schedules over a 28-day cycle. Both cohorts also received a single dose 4 days before Cycle 1.

What were the key safety and efficacy findings reported?

All treated patients experienced at least one treatment-emergent adverse event, with grade ≥3 events reported in a subset. One dose-limiting toxicity occurred in each cohort, and stable disease was observed as the best objective response in several patients.

Sep 28, 2026

Uploaded by Miles