Evidence map›Paper›PMID 40334082›Full record

Trial reportBlood advances2025

ADORE: an open platform study of ruxolitinib in combination with other novel therapies in patients with myelofibrosis.

David M Ross, Florian H Heidel, Andrew Charles Perkins, Andreas Reiter, Carl Crodel, Caroline Riley, María Teresa Gómez-Casares, Istvan Takacs, Heiko Becker, Thomas Lehmann and 13 more

Registry-linked trialAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in Blood advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04097821 (A Randomized, Open-label, Phase I/II Open Platform Study Evaluating Safety and Efficacy of Novel Ruxolitinib Combinations in Myelofibrosis Patients), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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.

NCT04097821 phase1 / phase2terminatednot on this map

A Randomized, Open-label, Phase I/II Open Platform Study Evaluating Safety and Efficacy of Novel Ruxolitinib Combinations in Myelofibrosis Patients

TypeinterventionalSponsorNovartis PharmaceuticalsRan2019 to 2024Enrolled45ConditionsMyelofibrosisArmsRuxolitinib, Siremadlin, Crizanlizumab, Sabatolimab, Rineterkib
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

23 authors.

David M RossDepartment of Haematology, Royal Adelaide Hospital and SA Pathology, Adelaide, Australia.ORCID 0000-0001-7171-2935
Florian H HeidelHematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.ORCID 0000-0003-2438-1955
Andrew Charles PerkinsAustralian Centre for Blood Diseases, Monash University and Alfred Hospital, Melbourne, VIC, Australia.ORCID 0000-0003-3644-7093
Andreas ReiterDepartment of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.ORCID 0000-0002-7718-6507
Carl CrodelKlinik für Innere Medizin II Abt. Hämatologie und Onkologie, Universitätsklinikum Jena, Jena, Germany.
Caroline RileyDepartment of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID 0009-0003-1431-086X
María Teresa Gómez-CasaresHospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Spain.ORCID 0000-0003-0505-5126
Istvan TakacsClinic of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary.ORCID 0000-0002-7810-4833
Heiko BeckerDepartment of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID 0000-0002-6919-4048
Thomas LehmannClinic for Medical Oncology and Hematology, Cantonal Hospital St Gallen, St Gallen, Switzerland.ORCID 0000-0002-5750-6876
Olga VinogradovaMoscow City Hematology Centre, Botkin Hospital, Moscow, Russia.ORCID 0000-0002-3669-0141
Kate BurburyDepartment of Haematology, Peter MacCallum Cancer Centre, Melbourne, Australia.
Alessandro M VannucchiCenter for Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy.ORCID 0000-0001-5755-0730
Vikas GuptaDepartment of Medicine, Princess Margaret Cancer Centre, Toronto, ON, Canada.ORCID 0000-0002-1419-8607
Marielle WondergemDepartment of Hematology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Jean-Jacques KiladjianDepartment of Hematology, Hôpital Saint-Louis and Université de Paris, Paris, France.ORCID 0000-0002-8121-438X
Grace ClearyNovartis Ireland Limited, Dublin, Ireland.
Angela ZhangNovartis Pharma AG, Basel, Switzerland.
Jagannath KotaNovartis Healthcare Pvt Ltd, Hyderabad, India.
Anirudh PrahalladNovartis Pharma AG, Basel, Switzerland.
Monika WroclawskaNovartis Pharma AG, Basel, Switzerland.
Min LuDivision of Hematology/Medical Oncology/Pathology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.ORCID 0000-0002-4191-4787
Claire N HarrisonGuy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractRuxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, is the standard of care for symptomatic patients with myelofibrosis (MF). However, ∼70% of patients discontinue ruxolitinib after ∼5 years, a third of whom report suboptimal splenic response. ADORE was a phase 1b/2 study with an innovative open platform design that assessed the safety, efficacy, and pharmacokinetics of novel compounds in combination with ruxolitinib in patients with MF who had a suboptimal response to ruxolitinib alone. A total of 44 patients were enrolled in part 1 of the study of ruxolitinib in combination with siremadlin, rineterkib, sabatolimab, crizanlizumab, or NIS793. Most patients were allocated to receive ruxolitinib plus siremadlin (N = 23). The most frequent adverse events with siremadlin were gastrointestinal (nausea and diarrhea) and hematological (thrombocytopenia, anemia, and neutropenia). Siremadlin 30 mg orally once daily on days 1 to 5 of a 28-day cycle was selected as the recommended phase 2 dose. The most robust spleen volume reduction (SVR) at 24 weeks was observed with ruxolitinib plus siremadlin 30 mg. Reductions in percent JAK2V617F allele burden at week 24 were observed, notably in several patients with SVR. An increase in growth differentiation factor 15 protein levels in patients receiving siremadlin demonstrated the on-target modulation of downstream p53 targets. Overall, available data from ADORE suggest the feasibility and benefits of combining novel agents with ruxolitinib in patients with suboptimal response to ruxolitinib alone. This trial was registered at www.clinicaltrials.gov as #NCT04097821.

Indexed as

Primary MyelofibrosisPyrazolesAdultAgedAged, 80 and overFemaleHumansJanus Kinase 2MaleMiddle AgedNitrilesPyrimidinesTreatment OutcomeJanus Kinase 2NitrilesPyrazolesPyrimidinesruxolitinib

Identifiers

PMID40334082
PMCPMC12362515

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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.