ArticleInvestigational new drugs2022
Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors.
Article in Investigational new drugs, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03225105 (A Phase I, Open-label, Uncontrolled, Multicenter, Dose-escalation Study of M3541 in Combination With Palliative Radiotherapy in Subjects With Solid Tumors), which is not on this map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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, Open-label, Uncontrolled, Multicenter, Dose-escalation Study of M3541 in Combination With Palliative Radiotherapy in Subjects With Solid Tumors
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- ATM is associated with the prognosis of colorectal cancer: a systematic review.Frontiers in oncology · 2025Pooled it
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Targeting ATR-CHK1 and ATM-CHK2 Axes in Pancreatic Cancer-A Comprehensive Review of Literature.International journal of molecular sciences · 2026Review
- IFI16 Enhances Chemosensitivity of Breast Cancer Cells by Inhibiting DNA Damage Response.Biomolecules & therapeutics · 2025Article
- The novel brain penetrant ataxia-telangiectasia mutated inhibitor WSD0628 provides robust radiosensitization of brain tumor patient-derived xenografts.Neuro-oncology · 2025Article
- The interplay of DNA damage, epigenetics and tumour heterogeneity in driving cancer cell fitness.Nature communications · 2025Review
- Prioritization of novel agents for further investigation in pediatric non-rhabdomyosarcoma soft tissue sarcomas: A report from the Children's Oncology Group.European journal of cancer (Oxford, England : 1990) · 2025Review
- Cancer Vulnerabilities Through Targeting the ATR/Chk1 and ATM/Chk2 Axes in the Context of DNA Damage.Cells · 2025Review
- Perspectives on cancer therapy-synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges.Cell death discovery · 2025Review
- The Development of ATM Inhibitors in Cancer Therapy.Targeted oncology · 2025Review
- Phosphorylated BLM peptide acts as an agonist for DNA damage response.Nucleic acids research · 2025Article
- Computer-aided Drug Discovery of Epigenetic Modulators in Dual-target Therapy of Multifactorial Diseases.Current topics in medicinal chemistry · 2025Review
- Genotype-Directed Synthetic Cytotoxicity of ATR Inhibition with Radiotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology.Neuro-oncology · 2024Review
- Preclinical Systemic Pharmacokinetics, Dose Proportionality, and Central Nervous System Distribution of the ATM Inhibitor WSD0628, a Novel Radiosensitizer for the Treatment of Brain Tumors.The Journal of pharmacology and experimental therapeutics · 2024Article
- TIPRL1 and its ATM-dependent phosphorylation promote radiotherapy resistance in head and neck cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Quantum-assisted fragment-based automated structure generator (QFASG) for small molecule design: anFrontiers in chemistry · 2024Article
- Advances in molecular targeted therapies to increase efficacy of (chemo)radiation therapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Review
- Detecting radio- and chemoresistant cells in 3D cancer co-cultures using chromatin biomarkers.Scientific reports · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAtaxia telangiectasia mutated (ATM) kinase orchestrates DNA double strand break (DSB) repair; ATM inhibitors may therefore enhance the therapeutic effect of DSB-inducing treatments such as radiotherapy (RT). M3541 is an orally administered selective inhibitor of ATM.
methodsThis phase I dose-escalation study evaluated the maximum-tolerated dose (MTD), recommended phase II dose(s) (RP2D), safety, pharmacokinetics (PK) and antitumor activity of M3541 in combination with fractionated palliative RT in patients with solid tumors. Fifteen patients received palliative RT (30 Gy in 10 fractions) and escalating doses of M3541 (50-300 mg administered on RT fraction days) guided by a Bayesian 2-parameter logistic regression model with overdose control.
resultsDoses of M3541 up to 300 mg/fraction day were well tolerated. One patient (200 mg group) experienced two dose-limiting toxicities (urinary tract infection, febrile neutropenia) that resolved with antibiotics. All patients reported ≥ 1 treatment-emergent adverse event (TEAE) but none led to treatment discontinuation. No grade ≥ 4 TEAEs were reported and there was no indication of a dose effect for any TEAE. Three patients (20.0%; 95% confidence interval 4.3-48.1) had confirmed complete or partial response. M3541 total plasma levels did not increase with dose following single or repeated dosing. No relationship was observed between dose and changes in the ratio of phosphorylated to total ATM or in immune cell counts.
conclusionsThe MTD and RP2D could not be established as the study closed early due to the absence of a dose-response relationship and non-optimal PK profile. No further clinical development of M3541 was pursued. (Trial registration number ClinicalTrials.gov NCT03225105. Registration date July 21, 2017).
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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.