ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
A phase I study of oral ARRY-614, a p38 MAPK/Tie2 dual inhibitor, in patients with low or intermediate-1 risk myelodysplastic syndromes.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 54 citations in OpenAlex.
- Trial
- Molecular biology of targeting lymphangiogenesis in cancer: Therapeutic strategies and future promise.Fundamental research · 2026Review
- Exploring the Bone Marrow Microenvironment as a Therapeutic Barrier and Targetable Source of Crosstalk in Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Review
- Molecular Insights and Therapeutic Advances in Low-Risk Myelodysplastic Neoplasms: A Clinical Review.Cancers · 2025Review
- Article
- Myelodysplastic syndromes: 2023 update on diagnosis, risk-stratification, and management.American journal of hematology · 2023Review
- Megakaryopoiesis impairment through acute innate immune signaling activation by azacitidine.The Journal of experimental medicine · 2022Article
- Review
- Pexmetinib suppresses osteoclast formation and breast cancer induced osteolysis via P38/STAT3 signal pathway.Journal of bone oncology · 2022Article
- The genetics of myelodysplastic syndromes and the opportunities for tailored treatments.Frontiers in oncology · 2022Review
- Methylation of dual-specificity phosphatase 4 controls cell differentiation.Cell reports · 2021Article
- Ang2 inhibitors and Tie2 activators: potential therapeutics in perioperative treatment of early stage cancer.EMBO molecular medicine · 2021Review
- Characterization and Cytotoxicity ofFrontiers in bioengineering and biotechnology · 2021Article
- Tetraspanin CD82 drives acute myeloid leukemia chemoresistance by modulating protein kinase C alpha and β1 integrin activation.Oncogene · 2020Article
- Transcriptomic analysis implicates necroptosis in disease progression and prognosis in myelodysplastic syndromes.Leukemia · 2020Article
- Flaming and fanning: The Spectrum of inflammatory influences in myelodysplastic syndromes.Blood reviews · 2019Review
- Small molecule purine and pseudopurine derivatives: synthesis, cytostatic evaluations and investigation of growth inhibitory effect in non-small cell lung cancer A549.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Phosphorylation of serine/arginine-rich splicing factor 1 at tyrosine 19 promotes cell proliferation in pediatric acute lymphoblastic leukemia.Cancer science · 2018Article
- Improving Treatment for Myelodysplastic Syndromes Patients.Current treatment options in oncology · 2018Review
- MAST1 Drives Cisplatin Resistance in Human Cancers by Rewiring cRaf-Independent MEK Activation.Cancer cell · 2018Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
purposeData suggest that activity of p38 MAPK and Tie2 kinases is dysregulated in myelodysplastic syndromes (MDS) and may be targets for novel therapies. A phase I study of ARRY-614, an oral dual inhibitor of p38 MAPK and Tie2, was conducted in patients with low or intermediate-1 International Prognostic Scoring System risk MDS to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary responses by International Working Group 2006 criteria. EXPERIMENTAL
designForty-five patients received ARRY-614 either once daily or twice daily in dose escalation (400, 600, 900, or 1,200 mg once daily; 200 or 300 mg twice daily) or expansion cohorts.
resultsThe 300 mg twice daily schedule was not tolerated, and an MTD was not reached for once daily dosing. Treatment-related adverse events were primarily grade 1-2, with the most common being rash, diarrhea, dry skin, fatigue and anorexia. Interpatient PK variability was high, although exposure was sufficient to achieve reduction in p38 MAPK activation in bone marrow and in the levels of circulating biomarkers. Disease responses were observed in 14 of 44 (32%) evaluable patients, 13 (93%) of whom had previously been treated with a hypomethylating agent. Responses were observed in all lineages, with 5 patients experiencing bilineage responses. Three of 25 red blood cell transfusion-dependent (TD) patients achieved transfusion independence (TI) and 5 of 7 platelet TD patients achieved TI.
conclusionsARRY-614 was well tolerated and has sufficient activity to warrant further evaluation in this patient population. We recommend 1,200 mg once daily as the optimal dose for further study.
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