Evidence map›Paper›PMID 30446007›Full record

ArticleJournal for immunotherapy of cancer2018

STAT3 antisense oligonucleotide AZD9150 in a subset of patients with heavily pretreated lymphoma: results of a phase 1b trial.

Matthew J Reilley, Patricia McCoon, Carl Cook, Paul Lyne, Razelle Kurzrock, Youngsoo Kim, Richard Woessner, Anas Younes, John Nemunaitis, Nathan Fowler and 17 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01563302 (A Phase 1/2 Study of ISIS 481464, an Antisense Oligonucleotide Inhibitor of STAT3, Administered to Patients With Advanced Cancers), which is not on this map. Cited by 174 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
174citing papers in PubMed, 2 pooled it
9.3field-weighted citation impact, top 1% of its field
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.

NCT01563302 phase1 / phase2completednot on this map

A Phase 1/2 Study of ISIS 481464, an Antisense Oligonucleotide Inhibitor of STAT3, Administered to Patients With Advanced Cancers

TypeinterventionalSponsorIonis Pharmaceuticals, Inc.Ran2012 to 2016Enrolled64ConditionsAdvanced Cancers, DLBCL, LymphomaArmsIONIS-STAT3Rx
3 · Its place in the literature

Who cites it

174 citing papers in PubMed, 2 syntheses or guidelines pooled it, 282 citations in OpenAlex.

  1. Pooled it
  2. STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review.Journal of experimental & clinical cancer research : CR · 2019
    Pooled it
  3. Trial
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  6. Article
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  9. Article
  10. Article
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  12. Article
  13. Advances in antisense oligonucleotide treatment for cancer.Japanese journal of clinical oncology · 2026
    Review
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  16. Review
  17. Article
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114 more citing papers are in PubMed but not listed here.

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

27 authors at 7 institutions in 2 countries.

Matthew J ReilleyDivision of Hematology/Oncology, University of Virginia Health System, Charlottesville, VA, USA.
Patricia McCoonOncology, IMED Biotech Unit, AstraZeneca Pharmaceuticals, Waltham, MA, USA.
Carl CookOncology, IMED Biotech Unit, AstraZeneca Pharmaceuticals, Waltham, MA, USA.
Paul LyneOncology, IMED Biotech Unit, AstraZeneca Pharmaceuticals, Waltham, MA, USA.
Razelle KurzrockUC San Diego Moores Cancer Center, La Jolla, CA, USA.
Youngsoo KimDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
Richard WoessnerOncology, IMED Biotech Unit, AstraZeneca Pharmaceuticals, Waltham, MA, USA.
Anas YounesMemorial Sloan Kettering Cancer Center, New York, NY, USA.
John NemunaitisMary Crowley Cancer Research Center, Dallas, TX, USA.
Nathan FowlerDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0455, Houston, TX, 77030, USA.
Michael CurranDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0455, Houston, TX, 77030, USA.
Qinying LiuDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0455, Houston, TX, 77030, USA.
Tianyuan ZhouDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
Joanna SchmidtDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
Minji JoDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
Samantha J LeeDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
Mason YamashitaDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
Steven G HughesDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
Luis FayadDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0455, Houston, TX, 77030, USA.
Sarina Piha-PaulDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0455, Houston, TX, 77030, USA.
Murali V P NadellaDrug Safety and Metabolism, IMED Biotech Unit, AstraZeneca Pharmaceuticals, Waltham, MA, USA.
Xiaokun XiaoDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
Jeff HsuDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
Alexey RevenkoDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
Brett P MoniaDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
A Robert MacLeodDepartment of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
David S HongDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0455, Houston, TX, 77030, USA. dshong@mdanderson.org.
Ionis Pharmaceuticals (United States) · USThe University of Texas MD Anderson Cancer Center · USAstraZeneca (Singapore) · SGMary Crowley Cancer Research Center · USMemorial Sloan Kettering Cancer Center · USMoores Cancer CenterPalmetto Hematology Oncology · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundThe Janus kinase (JAK) and signal transduction and activation of transcription (STAT) signaling pathway is an attractive target in multiple cancers. Activation of the JAK-STAT pathway is important in both tumorigenesis and activation of immune responses. In diffuse large B-cell lymphoma (DLBCL), the transcription factor STAT3 has been associated with aggressive disease phenotype and worse overall survival. While multiple therapies inhibit upstream signaling, there has been limited success in selectively targeting STAT3 in patients. Antisense oligonucleotides (ASOs) represent a compelling therapeutic approach to target difficult to drug proteins such as STAT3 through of mRNA targeting. We report the evaluation of a next generation STAT3 ASO (AZD9150) in a non-Hodgkin's lymphoma population, primarily consisting of patients with DLBCL.

methodsPatients with relapsed or treatment refractory lymphoma were enrolled in this expansion cohort. AZD9150 was administered at 2 mg/kg and the 3 mg/kg (MTD determined by escalation cohort) dose levels with initial loading doses in the first week on days 1, 3, and 5 followed by weekly dosing. Patients were eligible to remain on therapy until unacceptable toxicity or progression. Blood was collected pre- and post-treatment for analysis of peripheral immune cells.

resultsThirty patients were enrolled, 10 at 2 mg/kg and 20 at 3 mg/kg dose levels. Twenty-seven patients had DLBCL. AZD9150 was safe and well tolerated at both doses. Common drug-related adverse events included transaminitis, fatigue, and thrombocytopenia. The 3 mg/kg dose level is the recommended phase 2 dose. All responses were seen among DLBCL patients, including 2 complete responses with median duration of response 10.7 months and 2 partial responses. Peripheral blood cell analysis of three patients without a clinical response to therapy revealed a relative increase in proportion of macrophages, CD4+, and CD8+ T cells; this trend did not reach statistical significance.

conclusionsAZD9150 was well tolerated and demonstrated efficacy in a subset of heavily pretreated patients with DLBCL. Studies in combination with checkpoint immunotherapies are ongoing.

trial registrationRegistered at ClinicalTrials.gov: NCT01563302 . First submitted 2/13/2012.

Indexed as

AdultAgedAged, 80 and overFemaleHumansLymphomaMaleMiddle AgedOligonucleotidesOligonucleotides, AntisenseSTAT3 Transcription FactorYoung AdultdanvatirsenOligonucleotidesOligonucleotides, AntisenseSTAT3 protein, humanSTAT3 Transcription FactorAnti-sense oligonucleotideClinical trialDiffuse large B-cell lymphomaDLBCLImmunotherapyJAK-STATLymphomaSTAT3

Identifiers

PMID30446007
PMCPMC6240242
OpenAlexW2900450244

What OpenQuestion holds

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LicenceCC BY
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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.