ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
First-in-Human Study of the Ataxia Telangiectasia and Rad3-Related (ATR) Inhibitor Tuvusertib (M1774) as Monotherapy in Patients with Solid Tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04170153 (An Open-label, Multicenter Trial of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of Tuvusertib), which is not on this map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
An Open-label, Multicenter Trial of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of Tuvusertib (M1774) in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 301)
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- The efficacy and safety of ATR inhibitors in the treatment of solid tumors: a systematic review and meta-analysis.Frontiers in oncology · 2025Pooled it
- MONETTE: A Randomized Phase II Study of Ceralasertib plus Durvalumab or Ceralasertib Monotherapy in Patients with Advanced Melanoma Resistant to PD-(L)1 Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Trial
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- ATR inhibitors synergise with mitomycin C to enhance cytotoxicity in patient-derived non-muscle invasive bladder cancer organoids.British journal of cancer · 2026Article
- Paediatric therapeutic development workshop on osteosarcoma.British journal of cancer · 2026Review
- PTEN deficiency confers sensitivity to ATR inhibitor-based treatment in high-grade serous ovarian cancer.The Journal of clinical investigation · 2026Article
- Article
- Duocarmycin-Bearing Antibody-Mimetic Drug Conjugate Combined With an ATR Inhibitor Results in Complete Tumor Regression in a KPL-4 Xenograft Model.Cancer medicine · 2026Article
- Drugging non-canonical kinases in cancer therapeutics: Molecular targets, underlying mechanisms and small-molecule inhibitors.Acta pharmaceutica Sinica. B · 2026Review
- Structure Elucidation and Initial Characterization of a N-glucuronide Metabolite (M1) of Tuvusertib.European journal of drug metabolism and pharmacokinetics · 2026Article
- ATM counteracts chromatin-bound cGAS during DNA replication.Nature cell biology · 2026Article
- Genome-Scale CRISPR Screens Reveal DNA Repair Dependencies That Sensitize Hepatocellular Carcinoma to Oxaliplatin.Cancers · 2026Article
- Topoisomerase I inhibitor antibody-drug conjugates in breast cancer: the relevance of the DNA damage response to resistance, response, and combination treatment strategies.Breast cancer research and treatment · 2026Review
- Integrated Population Pharmacokinetic, Pharmacodynamic, and Safety Analyses to Inform Dosage Selection in the Clinical Development of the ATR Inhibitor Tuvusertib.Clinical pharmacology and therapeutics · 2026Article
- Targeting the DNA damage response prevents regrowth of colorectal peritoneal metastasis-derived organoids following treatment with mitomycin C.British journal of cancer · 2026Article
- Design, synthesis, and biological evaluation of aminopyrazine-based ATR/HDACs dual inhibitors.Molecular diversity · 2026Article
- An Integrated Nonclinical and Clinical Risk Assessment of the Effects of Investigational ATRi Tuvusertib on QTc Interval in Patients With Solid Tumors.Clinical and translational science · 2026Article
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- Pathway for the Development of ATR Inhibitors in Pediatric Malignancies: An ACCELERATE Multistakeholder Analysis.JCO precision oncology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 5 countries.
Funding
Abstract
purposeTuvusertib (M1774) is a potent, selective, orally administered ataxia telangiectasia and Rad3-related (ATR) protein kinase inhibitor. This first-in-human study (NCT04170153) evaluated safety, tolerability, maximum tolerated dose (MTD), recommended dose for expansion (RDE), pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of tuvusertib monotherapy. PATIENTS AND
methodsAscending tuvusertib doses were evaluated in 55 patients with metastatic or locally advanced unresectable solid tumors. A safety monitoring committee determined dose escalation based on PK, PD, and safety data guided by a Bayesian 2-parameter logistic regression model. Molecular responses (MR) were assessed in circulating tumor DNA samples.
resultsMost common grade ≥3 treatment-emergent adverse events were anemia (36%), neutropenia, and lymphopenia (both 7%). Eleven patients experienced dose-limiting toxicities, most commonly grade 2 (n = 2) or 3 (n = 8) anemia. No persistent effects on blood immune cell populations were observed. The RDE was 180 mg tuvusertib QD (once daily), 2 weeks on/1 week off treatment, which was better tolerated than the MTD (180 mg QD continuously). Tuvusertib median time to peak plasma concentration ranged from 0.5 to 3.5 hours and mean elimination half-life from 1.2 to 5.6 hours. Exposure-related PD analysis suggested maximum target engagement at ≥130 mg tuvusertib QD. Tuvusertib induced frequent MRs in the predicted efficacious dose range; MRs were enriched in patients with radiological disease stabilization, and complete MRs were detected for mutations in ARID1A, ATRX, and DAXX. One patient with platinum- and PARP inhibitor-resistant BRCA wild-type ovarian cancer achieved an unconfirmed RECIST v1.1 partial response.
conclusionsTuvusertib demonstrated manageable safety and exposure-related target engagement. Further clinical evaluation of tuvusertib is ongoing.
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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.