ArticleCancer chemotherapy and pharmacology2021
Population pharmacokinetics of ATR inhibitor berzosertib in phase I studies for different cancer types.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02157792 (An Open-Label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of VX-970/M6620 in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors), which is not on this map. Cited by 20 papers.
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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.
An Open-Label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of VX-970/M6620 in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors
Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- A hybrid PKPD agent-based model of the tumour immune interaction: effects of anti-cancer combination therapy.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Article
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Phase Ib study of berzosertib, carboplatin, gemcitabine, and pembrolizumab in patients with squamous nonsmall lung cancer (ETCTN 10313).The oncologist · 2025Article
- Article
- Microtracer-Based Assessment of the Mass Balance, Pharmacokinetics, and Excretion of [Clinical pharmacology in drug development · 2025Article
- A TRilogy of ATR's Non-Canonical Roles Throughout the Cell Cycle and Its Relation to Cancer.Cancers · 2024Review
- Asia-inclusive drug development leveraging principles of ICH E5 and E17 guidelines: Case studies illustrating quantitative clinical pharmacology as a foundational enabler.Clinical and translational science · 2024Review
- Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53-deficient myeloma cells.HemaSphere · 2024Article
- Integrating Artificial Intelligence for Drug Discovery in the Context of Revolutionizing Drug Delivery.Life (Basel, Switzerland) · 2024Review
- The ATR inhibitor berzosertib acts as a radio- and chemosensitizer in head and neck squamous cell carcinoma cell lines.Investigational new drugs · 2023Article
- Role of protein phosphorylation in cell signaling, disease, and the intervention therapy.MedComm · 2022Review
- Phase 1b study of berzosertib and cisplatin in patients with advanced triple-negative breast cancer.NPJ breast cancer · 2022Article
- Therapeutic advances in metastatic pancreatic cancer: a focus on targeted therapies.Therapeutic advances in medical oncology · 2022Review
- Review
- Ceralasertib (AZD6738), an Oral ATR Kinase Inhibitor, in Combination with Carboplatin in Patients with Advanced Solid Tumors: A Phase I Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Review
- Novel Insights into the Molecular Regulation of Ribonucleotide Reductase in Adrenocortical Carcinoma Treatment.Cancers · 2021Article
- Review
- Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress.Cancer cell · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeBerzosertib (formerly M6620) is the first-in-class inhibitor of ataxia-telangiectasia and Rad3-related protein, a key component of the DNA damage response, and being developed in combination with chemotherapy for the treatment of patients with advanced cancers. The objectives of this analysis were to characterize the pharmacokinetics (PK) of berzosertib across multiple studies and parts, estimate inter-individual variability, and identify covariates that could explain such variability.
methodsA population PK analysis was performed using the combined dataset from two phase I clinical studies (NCT02157792, EudraCT 2013-005100-34) in patients with advanced cancers receiving an intravenous infusion of berzosertib alone or in combination with chemotherapy. The analysis included data from 240 patients across 11 dose levels (18-480 mg/m
resultsPK data were best described by a two-compartment linear model. For a typical patient, the estimated clearance (CL) and intercompartmental CL were 65 L/h and 295 L/h, respectively, with central and peripheral volumes estimated to be 118 L and 1030 L, respectively. Several intrinsic factors were found to influence berzosertib PK, but none were considered clinically meaningful due to a very limited effect. Model simulations indicated that concentrations of berzosertib exceeded p-Chk1 (proximal pharmacodynamic biomarker) IC
conclusionsThere was no evidence of a clinically significant PK interaction between berzosertib and evaluated chemo-combinations. The covariate analysis did not highlight any need for dosing adjustments in the population studied to date. CLINICAL TRIAL INFORMATION: NCT02157792, EudraCT 2013-005100-34.
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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.