Evidence map›Paper›PMID 36156099›Full record

Trial reportThe oncologist2022

Epacadostat Plus Pembrolizumab and Chemotherapy for Advanced Solid Tumors: Results from the Phase I/II ECHO-207/KEYNOTE-723 Study.

John D Powderly, Samuel J Klempner, Aung Naing, Johanna Bendell, Ignacio Garrido-Laguna, Daniel V T Catenacci, Matthew H Taylor, James J Lee, Fred Zheng, Feng Zhou and 3 more

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

Trial report in The oncologist, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03085914 (A Phase 1/2, Open-Label, Safety, Tolerability, and Efficacy Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors), which is not on this map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.6field-weighted citation impact, top 17% 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.

NCT03085914 phase1 / phase2completednot on this map

A Phase 1/2, Open-Label, Safety, Tolerability, and Efficacy Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors (ECHO-207/KEYNOTE-723)

TypeinterventionalSponsorIncyte CorporationRan2017 to 2020Enrolled70ConditionsSolid TumorArmsEpacadostat, Pembrolizumab, Oxaliplatin, Leucovorin, 5-Fluorouracil
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 27 citations in OpenAlex.

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  16. Glioblastoma Therapy: Past, Present and Future.International journal of molecular sciences · 2024
    Review
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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

13 authors at 10 institutions in 1 country.

John D PowderlyCancer Research Clinic, Carolina BioOncology Institute, Huntersville, NC, USA.ORCID 0000-0002-7608-0380
Samuel J KlempnerDepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Aung NaingDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Johanna BendellDrug Development Unit, Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, USA.
Ignacio Garrido-LagunaDivision of Oncology, University of Utah School of Medicine, Huntsman Cancer Institute, Salt Lake City, UT, USA.
Daniel V T CatenacciDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Matthew H TaylorDivision of Hematology and Oncology, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
James J LeeCancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburg, PA, USA.
Fred ZhengIncyte Corporation, Wilmington, DE, USA.
Feng ZhouIncyte Corporation, Wilmington, DE, USA.
Xiaohua GongIncyte Corporation, Wilmington, DE, USA.
Hema GowdaIncyte Corporation, Wilmington, DE, USA.
Gregory L BeattyDepartment of Medicine, Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Incyte (United States) · USCarolina BioOncology Institute · USHarvard University · USProvidence Portland Medical Center · USSarah Cannon · USThe University of Texas MD Anderson Cancer Center · USUniversity of Chicago · USUniversity of Pennsylvania · USUniversity of Utah · USUPMC Hillman Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEpacadostat, an oral, selective inhibitor of IDO1, has shown activity when administered with pembrolizumab. We evaluated the addition of chemotherapy to epacadostat and pembrolizumab in patients with advanced or metastatic solid tumors. One proposed mechanism of resistance to PD-1 checkpoint inhibition is through immunosuppression mediated by L-kynurenine. IDO1, indoleamine-2,3-dioxygenase 1 is the rate-limiting enzyme catalyzing the conversion of L-tryptophan to L-kynurenine. If IDO1 is a mechanism of tumor escape from checkpoint inhibition, then addition of an IDO1 inhibitor with a PD-1 checkpoint inhibitor could enable tumor response to immunotherapy.

methodsPatients received one of 7 tumor-appropriate chemotherapy regimens. Pembrolizumab 200 mg was infused intravenously every 3 weeks. Epacadostat 100 mg was administered orally twice daily. The primary objectives of phase I were determining safety/tolerability and defining the maximum tolerated or pharmacologically active dose of epacadostat. Phase II of the study was designed to enroll efficacy-expansion cohorts and to assess changes in the tumor and tumor microenvironment via mandatory-biopsy cohorts.

resultsA total of 70 patients were enrolled. Twelve patients were enrolled in the phase II mandatory-biopsy cohorts. Due to early study closure, efficacy expansion did not enroll. Grades 3 and 4 treatment-emergent adverse events (TEAEs) occurred in 78.6% of patients. Neutropenia and disease progression were the only grades 3 and 4 TEAEs reported in ≥10.0% of patients. One treatment-related death was reported. The ORR was 31.4% across all treatment groups.

conclusionThe combination of epacadostat 100 mg bid with pembrolizumab and chemotherapy had an acceptable safety profile. This regimen showed antitumor activity across multiple types of advanced or metastatic solid tumors (ClinicalTrials.gov Identifier: NCT03085914).

Indexed as

KynurenineNeoplasmsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsHumansOximesProgrammed Cell Death 1 ReceptorSulfonamidesTumor MicroenvironmentAntibodies, Monoclonal, HumanizedepacadostatKynurenineOximespembrolizumabProgrammed Cell Death 1 ReceptorSulfonamidescancerchemotherapyepacadostatpembrolizumabsolid tumors

Identifiers

PMID36156099
PMCPMC9632315
OpenAlexW4297258937

What OpenQuestion holds

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LicenceCC BY-NC
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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.