ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2018
Phase I Study of ATR Inhibitor M6620 in Combination With Topotecan in Patients With Advanced Solid Tumors.
Registry-linked trialAbstract readClinical Trial, Phase I
In one paragraph
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02487095 (A Phase I/II Trial of Topotecan With VX-970), which is not on this map. Cited by 112 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% of its field
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.
A Phase I/II Trial of Topotecan With VX-970 (M6620), an ATR Kinase Inhibitor in Small Cell Cancers
Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 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
- Trial
- NCI 10211: a phase II, single-arm study of berzosertib in combination with irinotecan in patients with advanced TP53 mutant gastroesophageal cancer.The oncologist · 2025Trial
- A Phase II Single Arm Pilot Study of the CHK1 Inhibitor Prexasertib (LY2606368) in BRCA Wild-Type, Advanced Triple-Negative Breast Cancer.The oncologist · 2020Trial
- Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer.Cancer discovery · 2019Trial
- Safety and efficacy of ceralasertib, an ATR kinase inhibitor, combined with olaparib: dose escalation in advanced solid tumours and dose expansion in advanced breast cancer.British journal of cancer · 2026Article
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Molecular Determinants of Response and Rational Drug Combinations for Antibody-Drug Conjugates (ADCs) with Topoisomerase I (TOP1) Inhibitor Payloads.Journal of molecular biology · 2026Review
- Palladium-catalyzed Suzuki-Miyaura and Buchwald-Hartwig cross-coupling reactions towards the synthesis of pharmacologically potent pyrimidine-based molecules.Molecular diversity · 2026Review
- 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
- Multi-omics dissection of R-loop dynamics in tumorigenesis: From transcription-replication conflict to therapeutic targets.Molecular therapy. Oncology · 2026Review
- Replication origin flexibility: a tool to mitigate the hazards of excess replication.Trends in genetics : TIG · 2026Review
- Synthetic lethality in cancer: mechanism exploration and therapeutic applications.Cell communication and signaling : CCS · 2026Review
- Elimusertib enhances cytotoxic effects of conventional chemotherapy and sensitizes to radiation in preclinical Ewing sarcoma models.Scientific reports · 2026Article
- Article
- Targeting DNA Topoisomerase I for the Treatment of Cancer: Past, Present and Future.Journal of molecular biology · 2026Review
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- Article
- Deciphering TICRR's oncogenic landscape in pancreatic adenocarcinoma: molecular insights and clinical implications.Discover oncology · 2025Article
- Microtracer-Based Assessment of the Mass Balance, Pharmacokinetics, and Excretion of [Clinical pharmacology in drug development · 2025Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 1 institution in 1 country.
Anish ThomasAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Christophe E RedonAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Linda SciutoAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Emerson PadiernosAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Jiuping JiAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Min-Jung LeeAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Akira YunoAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Sunmin LeeAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Yiping ZhangAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Lan TranAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
William YutzyAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Arun RajanAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Udayan GuhaAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Haobin ChenAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Raffit HassanAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Christine C AlewineAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Eva SzaboAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Susan E BatesAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Robert J KindersAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Seth M SteinbergAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
James H DoroshowAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Mirit I AladjemAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Jane B TrepelAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Yves PommierAnish Thomas, Christophe E. Redon, Linda Sciuto, Emerson Padiernos, Min-Jung Lee, Akira Yuno, Sunmin Lee, Arun Rajan, Udayan Guha, Haobin Chen, Raffit Hassan, Christine C. Alewine, Eva Szabo, Seth M. Steinberg, James H. Doroshow, Mirit I. Aladjem, Jane B. Trepel, and Yves Pommier, National Cancer Institute, Bethesda; Jiuping Ji, Yiping Zhang, Lan Tran, William Yutzy, and Robert J. Kinders, Frederick National Laboratory for Cancer Research, Frederick, MD; and Susan E. Bates, Columbia University Medical Center, New York, NY.
Pancreatic Cancer Action Network · US
Funding
Exploiting DNA Replicative Stress for Novel Small Cell Lung Cancer TherapiesZIABC011793 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI THOMAS, ANISH · 2018 to 2025
$16.4MSignal Transduction Events and the Regulation of Cell GrowthZICSC006743 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI TREPEL, JANE B · 2009 to 2023
$13.8MDevelopment Therapeutics Branch Clinical TrialsZIABC011746 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 2017 to 2025
$2.6MClinical SupportZIEBC011653 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ALEWINE, CHRISTINE · 2015 to 2025
$218kIntramural NIH HHS ZIA BC011746Intramural NIH HHS ZIA BC011793
Abstract
Purpose Our preclinical work identified depletion of ATR as a top candidate for topoisomerase 1 (TOP1) inhibitor synthetic lethality and showed that ATR inhibition sensitizes tumors to TOP1 inhibitors. We hypothesized that a combination of selective ATR inhibitor M6620 (previously VX-970) and topotecan, a selective TOP1 inhibitor, would be tolerable and active, particularly in tumors with high replicative stress. Patients and Methods This phase I study tested the combination of M6620 and topotecan in 3-week cycles using 3 + 3 dose escalation. The primary end point was the identification of the maximum tolerated dose of the combination. Efficacy and pharmacodynamics were secondary end points. Results Between September 2016 and February 2017, 21 patients enrolled. The combination was well tolerated, which allowed for dose escalation to the highest planned dose level (topotecan 1.25 mg/m
Indexed as
AdultAgedAntineoplastic Combined Chemotherapy ProtocolsDose-Response Relationship, DrugDrug Administration ScheduleFemaleHumansIsoxazolesMaleMiddle AgedPyrazinesTopotecanTreatment OutcomeberzosertibIsoxazolesPyrazinesTopotecan
Identifiers
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Registered trials
NCT02487095ClinicalTrials.gov
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.