Evidence mapPaperPMID 42498485Full record

Trial reportJournal for immunotherapy of cancer2026

Durable responses to triplet immunotherapy targeting TGF-β, PD-L1, and tumor antigen, with an IL-15 receptor superagonist in mismatch repair proficient castration-resistant prostate cancer.

Jason Mark Redman, Ravi A Madan, Renee N Donahue, Nicole J Toney, Fatima Karzai, Julius Strauss, Claudia Palena, Lucas A Horn, Jaydira Del Rivero, Jennifer L Marté and 7 more

Registry-linked trialAbstract readClinical Trial, Phase IClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03493945 (A Phase I/II Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, N-803 and Epacadostat), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
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.

NCT03493945 phase1 / phase2completednot on this map

A Phase I/II Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, N-803 and Epacadostat (QuEST1)

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2018 to 2024Enrolled59ConditionsMetastatic Castration-resistant Prostate Cancer, Prostate Cancer, Prostate Neoplasm, Advanced Solid TumorArmsM7824, N-803, MVA-BN-Brachyury, FPV-Brachyury, Epacadostat
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

17 authors.

Jason Mark Redman *Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0001-8200-0167
Ravi A Madan *Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0001-5106-8636
Renee N Donahue *Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0002-6828-3073
Nicole J ToneyCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0003-4181-5647
Fatima KarzaiGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0002-3244-1332
Julius StraussCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Claudia PalenaCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0002-0445-4486
Lucas A HornCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0001-6011-2061
Jaydira Del RiveroDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Jennifer L MartéCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0009-0002-2567-8080
Lisa CordesCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0003-3833-4084
Megan T LynchCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0003-4805-9610
Thomas J MeyerCCR Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0002-7185-5597
Margaret CamCCR Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Patrick Soon-ShiongImmunityBio Inc, San Diego, California, USA.
Jeffrey SchlomCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0001-7932-4072
James L GulleyCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA gulleyj@mail.nih.gov.ORCID http://orcid.org/0000-0002-6569-2912

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImmune checkpoint blockade is minimally active in unselected castration-resistant prostate cancer (CRPC) and does not reproducibly yield durable decreases in prostate-specific antigen (PSA) levels.

methodsThe Quick Efficacy Seeking Trial was designed to employ a combination of agents to initiate an immune response (with BN-Brachyury vaccine), potentiate that response (with nogapendekin-alfa inbakicept (NAI), an interleukin (IL)-15 receptor superagonist), and reduce or eliminate immunosuppressive entities in the tumor microenvironment (with bintrafusp alfa, a dual inhibitor of programmed death-ligand 1 and transforming growth factor beta). Epacadostat (an indoleamine 2,3-dioxygenase (IDO) inhibitor) was also employed in one cohort to reduce immune suppression induced by IDO's conversion of tryptophan to kynurenine.

resultsPatients with CRPC enrolled sequentially to receive vaccine + bintrafusp alfa (Arm 2.1), vaccine + bintrafusp alfa + NAI (Arm 2.2), and vaccine + bintrafusp alfa + NAI + epacadostat (Arm 2.3), with the primary objective to determine response rate. Adverse events in Arms 2.1 and 2.2 were manageable and consistent with the safety profiles of each agent individually, and notable for five individuals developing isolated adrenocorticotropic hormone deficiency. Arm 2.3 was closed early due to skin toxicity. Sustained declines in PSA were seen in 1/13 (8%) patients in Arm 2.1, 7/24 (29%) patients in Arm 2.2, including six with proficient mismatch repair/microsatellite stable tumors, and 0/6 (0%) patients in Arm 2.3.

conclusionsAnalyses of peripheral immune profiles provided evidence of a multifaceted antitumor immune response, including IL-15 receptor superagonist NAI-dependent expansion and activation of natural killer cells and CD8 TRIAL REGISTRATION NUMBER: NCT03493945.

Indexed as

Antigens, NeoplasmB7-H1 AntigenImmunotherapyProstatic Neoplasms, Castration-ResistantTransforming Growth Factor betaAgedDNA Mismatch RepairHumansMaleMiddle AgedAntigens, NeoplasmB7-H1 AntigenTransforming Growth Factor betaCombination therapyCytokineImmunotherapyProstate CancerVaccine

Identifiers

PMID42498485
PMCPMC13410698

What Socratic 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 Socratic graph.