Investigational Drug
Ceralasertib
TrialFetch AI Analysis
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Overview
Ceralasertib (AZD6738) is an investigational oral cancer drug studied alone and with treatments including durvalumab. Human trials have reported responses, but results vary substantially by cancer type and study; its clinical benefit is not yet established. (pmc.ncbi.nlm.nih.gov)
Mechanism of action
Ceralasertib inhibits ATR, a kinase that helps cells respond to DNA damage and replication stress. Blocking ATR can impair DNA repair and cell-cycle checkpoints, potentially making susceptible cancer cells accumulate lethal damage. (pmc.ncbi.nlm.nih.gov)
Efficacy
- Monotherapy: In a phase II study of ARID1A-deficient solid tumors, 4 of 29 evaluable patients responded (14%); all four responses occurred in endometrioid endometrial or ovarian clear-cell cancer. In a separate phase IIa study of ATM-altered cancers, 2 of 28 patients with advanced solid tumors responded (7.1%). (aacrjournals.org)
- With durvalumab: A phase II lung-cancer study reported responses in 11 of 79 patients (13.9%). Results in previously treated melanoma have been inconsistent: one 30-patient study reported about 30%, whereas the later randomized MONETTE study reported 9.3% with the combination and 5.8% with ceralasertib alone; the combination did not meet its prespecified response threshold. These figures come from different populations and should not be treated as a direct comparison. (nature.com)
Safety
Low blood counts are an important toxicity, particularly anemia and thrombocytopenia; nausea and fatigue are also reported. In the first-in-human monotherapy study, intermittent dosing was better tolerated than continuous dosing, and no treatment-related deaths were reported. In MONETTE, grade 3 or higher adverse events of any cause occurred in 35.1% of combination-treated patients and 30.8% of monotherapy patients. (pmc.ncbi.nlm.nih.gov)
Further reading
- First-in-human monotherapy study
- ARID1A-deficient tumors: phase II study
- MONETTE randomized melanoma study
- HUDSON lung-cancer study
Last updated: Sep 2026
Active trials using Ceralasertib
Found 4 active trials using this drug:
TrialFetch AI summary: Adults with extensive-stage SCLC who complete first-line platinum–etoposide plus durvalumab without progression are assigned by tumor subtype and SLFN11 status to maintenance durvalumab alone or durvalumab plus a biomarker-directed agent. The added agent is saruparib (PARP1 inhibitor), ceralasertib (ATR inhibitor), or monalizumab (NKG2A-blocking antibody), depending on the assigned cohort.
ClinicalTrials.gov ID: NCT06769126
TrialFetch AI summary: Adults with previously treated, unresectable or metastatic HER2-expressing or HER2-amplified solid tumors receive trastuzumab deruxtecan, a HER2-directed antibody–drug conjugate carrying a topoisomerase I inhibitor, plus the oral ATR inhibitor ceralasertib. Expansion cohorts are limited to patients with gastroesophageal or colorectal cancer and a biopsiable lesion.
ClinicalTrials.gov ID: NCT04704661
TrialFetch AI summary: Adults with previously untreated extensive-stage small cell lung cancer, ECOG 0–1, and measurable disease receive four cycles of platinum–etoposide plus durvalumab, followed by maintenance durvalumab and investigational ceralasertib, an ATR inhibitor targeting the DNA-damage response. Treated, stable brain metastases are permitted.
ClinicalTrials.gov ID: NCT04699838
TrialFetch AI summary: Women with HER2-negative, germline BRCA-mutated advanced or metastatic breast cancer who have progressed after at least two months of PARP inhibitor therapy are randomized to olaparib plus cediranib, a VEGFR1–3 inhibitor, or olaparib plus ceralasertib, an ATR inhibitor.
ClinicalTrials.gov ID: NCT04090567
