Evidence map›Paper›PMID 38710487›Full record

Trial reportJournal of the National Cancer Institute2024

Ataxia telangiectasia and Rad3-related (ATR) inhibitor camonsertib dose optimization in patients with biomarker-selected advanced solid tumors (TRESR study).

Elisa Fontana, Ezra Rosen, Elizabeth K Lee, Martin Højgaard, Niharika B Mettu, Stephanie Lheureux, Benedito A Carneiro, Gregory M Cote, Louise Carter, Ruth Plummer and 9 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of the National Cancer Institute, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04497116 (Phase 1/2a Study of the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of RP-3500 Alone or in Combination With Talazoparib or Gemcitabine in Advanced Solid Tumors With ATR Inhibitor Sensitizing Mutations), which is not on this map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

NCT04497116 phase1 / phase2completednot on this map

Phase 1/2a Study of the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of RP-3500 Alone or in Combination With Talazoparib or Gemcitabine in Advanced Solid Tumors With ATR Inhibitor Sensitizing Mutations (TRESR Study)

TypeinterventionalSponsorRepare TherapeuticsRan2020 to 2025Enrolled276ConditionsAdvanced Solid TumorArmsRP-3500 (camonsertib), Talazoparib, Gemcitabine Injection
3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Camonsertib, an ATRi, in Combination with Low-Dose Gemcitabine in Solid Tumors with DNA Damage Response Aberrations: Preclinical and Phase Ib Results.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Elisa FontanaSarah Cannon Research Institute UK, London, UK.ORCID 0000-0002-4991-9355
Ezra RosenEarly Drug Development and Breast Medicine Services, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Elizabeth K LeeMedical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Martin HøjgaardDepartment of Oncology, Rigshospitalet, Copenhagen, Denmark.
Niharika B MettuMedical Oncology, Duke University, Durham, NC, USA.
Stephanie LheureuxPrincess Margaret Cancer Centre, Toronto, ON, Canada.
Benedito A CarneiroLegorreta Cancer Center at Brown University and Lifespan Cancer Institute, Division of Hematology/Oncology, Department of Medicine, The Warren Alpert Medical School, Brown University, Providence, RI, USA.
Gregory M CoteMass General Cancer Center, Boston, MA, USA.ORCID 0000-0003-0181-886X
Louise CarterDivision of Cancer Sciences, The University of Manchester, Manchester, UK.
Ruth PlummerSir Bobby Robson Cancer Trials Research Centre, Freeman Hospital, Newcastle upon Tyne, UK.ORCID 0000-0003-0107-1444
Devalingam MahalingamRobert H. Lurie Comprehensive Cancer Center, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Adrian J FretlandRepare Therapeutics, Cambridge, MA, USA.
Joseph D SchonhoftRepare Therapeutics, Cambridge, MA, USA.
Ian M SilvermanRepare Therapeutics, Cambridge, MA, USA.
Marisa WainszelbaumRepare Therapeutics, Cambridge, MA, USA.
Yi XuRepare Therapeutics, Cambridge, MA, USA.
Danielle UlanetRepare Therapeutics, Cambridge, MA, USA.
Maria KoehlerRepare Therapeutics, Cambridge, MA, USA.
Timothy A YapInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748Repare Therapeutics, Inc
6 · The paper itself

Abstract

backgroundCamonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus, dose and schedule optimization requires extended follow-up to assess prolonged treatment effects.

methodsLong-term safety, tolerability, and antitumor efficacy of 3 camonsertib monotherapy dosing regimens were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on, 4 days off (160 3/4; the preliminary recommended Phase II dose [RP2D]) and two step-down groups of 120 mg QD 3/4 (120 3/4) and 160 mg QD 3/4, 2 weeks on, 1 week off (160 3/4, 2/1w). Safety endpoints included incidence of treatment-related adverse events (TRAEs), dose modifications, and transfusions. Efficacy endpoints included overall response rate, clinical benefit rate, progression-free survival, and circulating tumor DNA (ctDNA)-based molecular response rate.

resultsThe analysis included 119 patients: 160 3/4 (n = 67), 120 3/4 (n = 25), and 160 3/4, 2/1w (n = 27) treated up to 117.1 weeks as of the data cutoff. The risk of developing grade 3 anemia was significantly lower in the 160 3/4, 2/1w group compared with the preliminary RP2D group (hazard ratio = 0.23, 2-sided P = .02), translating to reduced transfusion and dose reduction requirements. The intermittent weekly schedule did not compromise antitumor activity.

conclusionThe 160 3/4, 2/1w dose was established as an optimized regimen for future camonsertib monotherapy studies offering a substantial reduction in the incidence of anemia without any compromise to efficacy. CLINICAL TRIAL ID: NCT04497116.

Indexed as

Ataxia Telangiectasia Mutated ProteinsNeoplasmsAdultAgedAged, 80 and overBiomarkers, TumorDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedProtein Kinase InhibitorsAtaxia Telangiectasia Mutated ProteinsATR protein, humanBiomarkers, TumorProtein Kinase Inhibitors

Identifiers

PMID38710487
PMCPMC11378309

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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.