Trial reportBritish journal of cancer2025
The DNA-PK inhibitor AZD7648 alone or combined with pegylated liposomal doxorubicin in patients with advanced cancer: results of a first-in-human Phase I/IIa study.
Trial report in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03907969 (A Phase I/IIa, Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD7648 Monotherapy or in Combination With Either Cytotoxic Chemotherapies or Novel Anti-Cancer Agents in Patients With Advanced Malignancies), which is not on this map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I/IIa, Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD7648 Monotherapy or in Combination With Either Cytotoxic Chemotherapies or Novel Anti-Cancer Agents in Patients With Advanced Malignancies
Who cites it
9 citing papers in PubMed.
- Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review).Oncology reports · 2026Review
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in theMolecular therapy. Nucleic acids · 2026Article
- Targeting DNA-PK: medicinal chemistry insights into small-molecule inhibitor discovery and optimisation.RSC medicinal chemistry · 2026Review
- Drugging non-canonical kinases in cancer therapeutics: Molecular targets, underlying mechanisms and small-molecule inhibitors.Acta pharmaceutica Sinica. B · 2026Review
- Synergistic Effects of DNA-PKcs Inhibition and Radiotherapy in Esophageal Squamous Cell Carcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Impeding the NHEJ Pathway for Overcoming Radioresistance in the Context of Precision Radiotherapy of Cancer.Pharmaceutics · 2026Review
- Targeting DNA Damage Repair Pathways Beyond PARP Inhibition.Targeted oncology · 2025Review
- The interplay of DNA damage, epigenetics and tumour heterogeneity in driving cancer cell fitness.Nature communications · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
backgroundUpregulation of DNA-dependent protein kinase (DNA-PK) is associated with poor prognosis and decreased response to DNA-damaging agents across cancer types. A Phase I/IIa study (NCT03907969) investigated the highly potent, selective DNA-PK inhibitor AZD7648 as monotherapy or combined with pegylated liposomal doxorubicin (PLD) in patients with advanced cancer.
methodsThirty patients received escalating doses of AZD7648 as monotherapy (n = 14), starting at 5 mg QD, or with PLD 40 mg/m
resultsAZD7648 monotherapy was administered at 5-160 mg BID. The most frequent class of adverse events was gastrointestinal disorders (9/14 patients, 64.3%); one patient (160 mg BID) experienced dose-limiting toxicities (DLTs). No responses to AZD7648 monotherapy were observed. The maximum dose of combination therapy was AZD7648 40 mg QD days 1-7 + PLD every 28 days. 13/16 patients (81.3%) experienced gastrointestinal disorders and 11/16 (68.8%) patients had anaemia. Three patients experienced DLTs (two at AZD7648 20 mg QD 7 days + PLD; one at AZD7648 30 mg QD 7 days + PLD). Limited efficacy was observed, with one RECIST partial response. DISCUSSION: Toxicity of AZD7648 + PLD was greater than expected and antitumour activity was limited, leading to early study termination.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.