Ceralasertib, an ATR kinase inhibitor, as monotherapy in Japanese patients with advanced solid malignancies: Results from a phase 1 study

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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, NCT05469919. Registration date: May 18, 2022.

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