Evidence map›Paper›PMID 29921320›Full record

Trial reportJournal for immunotherapy of cancer2018

Phase Ia study of the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor navoximod (GDC-0919) in patients with recurrent advanced solid tumors.

Asha Nayak-Kapoor, Zhonglin Hao, Ramses Sadek, Robin Dobbins, Lisa Marshall, Nicholas N Vahanian, W Jay Ramsey, Eugene Kennedy, Mario R Mautino, Charles J Link and 11 more

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

Trial report 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 NCT02048709 (A Phase I Study of GDC-0919 for Adult Patients With Recurrent Advanced Solid Tumors), which is not on this map. Cited by 90 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 3 pooled it
4.8field-weighted citation impact, top 3% 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.

NCT02048709 phase1completednot on this map

A Phase I Study of GDC-0919 for Adult Patients With Recurrent Advanced Solid Tumors

TypeinterventionalSponsorGenentech, Inc.Ran2014 to 2016Enrolled22ConditionsSolid TumorArmsGDC-0919
3 · Its place in the literature

Who cites it

90 citing papers in PubMed, 3 syntheses or guidelines pooled it, 150 citations in OpenAlex.

  1. Pooled it
  2. The immunotherapeutic role of indoleamine 2,3-dioxygenase in head and neck squamous cell carcinoma: A systematic review.Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery · 2021
    Pooled it
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30 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

21 authors at 2 institutions in 1 country.

Asha Nayak-KapoorGeorgia Cancer Center at Augusta University, Augusta, GA, USA.
Zhonglin HaoGeorgia Cancer Center at Augusta University, Augusta, GA, USA.
Ramses SadekGeorgia Cancer Center at Augusta University, Augusta, GA, USA.
Robin DobbinsGeorgia Cancer Center at Augusta University, Augusta, GA, USA.
Lisa MarshallGeorgia Cancer Center at Augusta University, Augusta, GA, USA.
Nicholas N VahanianNewLink Genetics, Ames, IA, USA.
W Jay RamseyNewLink Genetics, Ames, IA, USA.
Eugene KennedyNewLink Genetics, Ames, IA, USA.
Mario R MautinoNewLink Genetics, Ames, IA, USA.
Charles J LinkNewLink Genetics, Ames, IA, USA.
Ray S LinGenentech, Inc., South San Francisco, CA, USA.
Stephanie Royer-JooGenentech, Inc., South San Francisco, CA, USA.
Xiaorong LiangGenentech, Inc., South San Francisco, CA, USA.
Laurent SalphatiGenentech, Inc., South San Francisco, CA, USA.
Kari M MorrisseyGenentech, Inc., South San Francisco, CA, USA.
Sami MahrusGenentech, Inc., South San Francisco, CA, USA.
Bruce McCallGenentech, Inc., South San Francisco, CA, USA.
Andrea PirzkallGenentech, Inc., South San Francisco, CA, USA.
David H MunnGeorgia Cancer Center at Augusta University, Augusta, GA, USA.
John E JanikGeorgia Cancer Center at Augusta University, Augusta, GA, USA.
Samir N KhleifGeorgia Cancer Center at Augusta University, Augusta, GA, USA. snk48@georgetown.edu.
Augusta University Health · USNewLink Genetics (United States) · US

Funding

Reprogramming the TME for immunogenic antigen-presentationR01CA103320 · NCI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI MUNN, DAVID H. · 2003 to 2024
$6.0M
PTEN, Tregs and MDSCs in the tumor microenvironmentR01CA211229 · NCI · AUGUSTA UNIVERSITY · PI MUNN, DAVID H. · 2017 to 2021
$1.7M
NCI NIH HHS R01 CA103320NCI NIH HHS R01 CA211229
6 · The paper itself

Abstract

backgroundIndoleamine-2,3-dioxygenase 1 (IDO1) catalyzes the oxidation of tryptophan into kynurenine and is partially responsible for acquired immune tolerance associated with cancer. The IDO1 small molecule inhibitor navoximod (GDC-0919, NLG-919) is active as a combination therapy in multiple tumor models.

methodsThis open-label Phase Ia study assessed safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of navoximod in patients with recurrent/advanced solid tumors, administered as 50-800 mg BID on a 21/28 day and at 600 mg on a 28/28 day schedule. Plasma kynurenine and tryptophan were longitudinally evaluated and tumor assessments were performed.

resultsPatients (n = 22) received a median of 3 cycles of navoximod. No maximum tolerated dose was reached. One dose-limiting toxicity of Grade 4 lower gastrointestinal hemorrhage was reported. Adverse events (AEs) regardless of causality in ≥20% of patients included fatigue (59%), cough, decreased appetite, and pruritus (41% each), nausea (36%), and vomiting (27%). Grade ≥ 3 AEs occurred in 14/22 patients (64%), and were related to navoximod in two patients (9%). Navoximod was rapidly absorbed (T

conclusionsNavoximod was well-tolerated at doses up to 800 mg BID decreasing plasma kynurenine levels consistent with its half-life. Stable disease responses were observed.

trial registrationClinicalTrials.gov identifier: NCT02048709 .

Indexed as

AgedAged, 80 and overBiomarkers, TumorEnzyme InhibitorsFemaleHumansIndoleamine-Pyrrole 2,3,-DioxygenaseMaleMiddle AgedNeoplasm MetastasisNeoplasmsNeoplasm StagingRecurrenceTreatment OutcomeBiomarkers, TumorEnzyme InhibitorsIndoleamine-Pyrrole 2,3,-DioxygenaseIDO1KynurenineNavoximodPhase ITryptophan

Identifiers

PMID29921320
PMCPMC6009946
OpenAlexW2809526912

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.