Evidence map›Paper›PMID 35288468›Full record

ArticleJournal for immunotherapy of cancer2022

Exploring the safety, effect on the tumor microenvironment, and efficacy of itacitinib in combination with epacadostat or parsaclisib in advanced solid tumors: a phase I study.

Aung Naing, John D Powderly, John J Nemunaitis, Jason J Luke, Aaron S Mansfield, Wells A Messersmith, Solmaz Sahebjam, Patricia M LoRusso, Ignacio Garrido-Laguna, Lance Leopold and 4 more

Erratum issued 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, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02559492 (A Platform Study Exploring the Safety, Tolerability, Effect on the Tumor Microenvironment, and Efficacy of INCB Combinations in Advanced Solid Tumors), which is not on this map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.1field-weighted citation impact, top 12% 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.

NCT02559492 phase1terminatednot on this map

A Platform Study Exploring the Safety, Tolerability, Effect on the Tumor Microenvironment, and Efficacy of INCB Combinations in Advanced Solid Tumors

TypeinterventionalSponsorIncyte CorporationRan2015 to 2019Enrolled142ConditionsSolid TumorsArmsItacitinib, Epacadostat, INCB050465
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 12 institutions in 1 country.

Aung NaingDepartment of Investigational Cancer Therapeutics, MD Anderson Cancer Center, Houston, Texas, USA anaing@mdanderson.org.ORCID 0000-0002-4803-8513
John D PowderlyCancer Research Clinic, Carolina Biooncology Institute, Huntersville, North Carolina, USA.ORCID 0000-0002-7608-0380
John J NemunaitisUniversity of Toledo College of Medicine, Toledo, Ohio, USA.ORCID 0000-0002-2234-2381
Jason J LukeDivision of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.ORCID 0000-0002-1182-4908
Aaron S MansfieldOncology, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0002-9483-6903
Wells A MessersmithSchool of Medicine, University of Colorado, Aurora, Colorado, USA.
Solmaz SahebjamClinical Research Unit, Moffitt Cancer Center, Tampa, Florida, USA.
Patricia M LoRussoYale School of Medicine, Yale Cancer Center, New Haven, Connecticut, USA.
Ignacio Garrido-LagunaUniversity of Utah School of Medicine, Huntsman Cancer Institute, Salt Lake City, Utah, USA.ORCID 0000-0003-2273-9028
Lance LeopoldImmuno-Oncology, Incyte Corporation, Wilmington, Delaware, USA.
Ryan GeschwindtImmuno-Oncology, Incyte Corporation, Wilmington, Delaware, USA.
Kai DingBiostatistics, Incyte Corporation, Wilmington, Delaware, USA.
Michael SmithImmuno-Oncology, Incyte Corporation, Wilmington, Delaware, USA.
Jordan D BerlinDivision of Hematology/Oncology, Vanderbilt University, Nashville, Tennessee, USA.
Incyte (United States) · USCancer Research And Biostatistics · USCarolina BioOncology Institute · USMayo Clinic · USMoffitt Cancer Center · USPalmetto Hematology Oncology · USThe University of Texas MD Anderson Cancer Center · USUniversity of Colorado System · USUniversity of Toledo · USUniversity of Utah · USVanderbilt University · USYale Cancer Center · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
NCI NIH HHS P30 CA015083
6 · The paper itself

Abstract

backgroundThis phase I multicenter study was designed to evaluate the safety, tolerability, efficacy, and translational effects on the tumor microenvironment of itacitinib (Janus-associated kinase 1 (JAK1) inhibitor) in combination with epacadostat (indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor) or parsaclisib (phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor).

methodsPatients with advanced or metastatic solid tumors were enrolled and received itacitinib (100-400 mg once a day) plus epacadostat (50-300 mg two times per day; group A), or itacitinib (100-400 mg once a day) plus parsaclisib or parsaclisib monotherapy (0.3-10 mg once a day; group B).

resultsA total of 142 patients were enrolled in the study. The maximum tolerated dose was not reached for either the combination of itacitinib plus epacadostat (n=47) or itacitinib plus parsaclisib (n=90). One dose-limiting toxicity of serious, grade 3 aseptic meningitis was reported in a patient receiving itacitinib 300 mg once a day plus parsaclisib 10 mg once a day, which resolved when the study drugs were withdrawn. The most common treatment-related adverse events among patients treated with itacitinib plus epacadostat included fatigue, nausea, pyrexia, and vomiting, and for patients treated with itacitinib plus parsaclisib were fatigue, pyrexia, and diarrhea. In the itacitinib plus epacadostat group, no patient had an objective response. Among patients receiving itacitinib 100 mg once a day plus parsaclisib 0.3 mg once a day, three achieved partial response for an objective response rate (95% CI) of 7.1% (1.50 to 19.48). Treatment with itacitinib plus epacadostat demonstrated some increase in tumor CD8

conclusionAdverse events with JAK1 inhibition combined with either IDO1 or PI3Kδ inhibition were manageable, but the combinations demonstrated limited clinical activity or enhancement of immune activation in the tumor microenvironment. TRIAL REGISTRATION NUMBER: NCT02559492.

Indexed as

NeoplasmsTumor MicroenvironmentAcetonitrilesHumansOximesPyrazolesPyrimidinesPyrrolesPyrrolidinesSulfonamidesAcetonitrilesepacadostatitacitinibOximesparsaclisibPyrazolesPyrimidinesPyrrolesPyrrolidinesSulfonamidesbiomarkers, tumorclinical trials as topicdrug therapy, combinationimmunomodulationtumor microenvironment

Identifiers

PMID35288468
PMCPMC8921936
OpenAlexW4221026187

What OpenQuestion holds

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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.