Evidence map›Paper›PMID 41099363›Full record

Trial reportNeuro-oncology2026

Phase I/II and window-of-opportunity study of pamiparib and metronomic temozolomide for recurrent isocitrate dehydrogenase mutant gliomas.

David Schiff, Xiaobu Ye, Jing Li, Benjamin M Ellingson, Patrick Y Wen, Tobias Walbert, Jian Campian, Louis B Nabors, Byram H Ozer, Arati Desai and 5 more

Abstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Recent Advances in Targeted Therapies for Adult Gliomas.Current neurology and neuroscience reports · 2026
    Review
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

15 authors.

David SchiffDivision of Neuro-Oncology, University of Virginia School of Medicine, Charlottesville (D.S.).ORCID 0000-0002-1896-2502
Xiaobu YeDepartment of Neurosurgery, Johns Hopkins School of Medicine, Baltimore.
Jing LiDepartment of Oncology, Wayne State University, Detroit.
Benjamin M EllingsonDepartment of Radiological Sciences, David Geffen School of Medicine, UCLA, Los Angeles.ORCID 0000-0002-2764-6640
Patrick Y WenNeuro-Oncology Center, Dana-Farber Cancer Institute, Boston.
Tobias WalbertHermelin Brain Tumor Center, Henry Ford Hospital, Detroit.ORCID 0000-0003-0667-8106
Jian CampianDepartment of Neurology, Washington University School of Medicine, St Louis.
Louis B NaborsDepartment of Neurology, University of Alabama at Birmingham, Birmingham.
Byram H OzerDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore.
Arati DesaiDepartment of Medical Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Antonio OmuroDepartment of Neurology, Yale School of Medicine, New Haven.ORCID 0000-0003-4299-3664
Serena DesideriDepartment of Oncology, Johns Hopkins School of Medicine, Baltimore.
Neeraja DandaDepartment of Oncology, Johns Hopkins School of Medicine, Baltimore.
Stuart GrossmanDepartment of Oncology, Johns Hopkins School of Medicine, Baltimore.
Ranjit S BindraDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven.ORCID 0000-0002-3255-0467

Funding

Investigator Development CoreP50MD017338 · NIMHD · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MEHTA, TAPAN S · 2021 to 2025
$27.7M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI David A. Nathanson · 2017 to 2026
$25.2M
Adult Brain Tumor Consortium (ABTC)U01CA137443 · NCI · JOHNS HOPKINS UNIVERSITY · PI GROSSMAN, STUART A, PRADOS, MICHAEL D · 2009 to 2013
$11.0M
Adult Brain Tumor Consortium (ABTC)UM1CA137443 · NCI · JOHNS HOPKINS UNIVERSITY · PI GROSSMAN, STUART A · 2014 to 2020
$9.7M
Gateway for Cancer Research and Adult Brain Tumor Consortium UM1CA137443NCI NIH HHS P50 CA211015NCI NIH HHS U01 CA137443NCI NIH HHS UM1 CA137443NIMHD NIH HHS P50 MD017338
6 · The paper itself

Abstract

backgroundPreclinical studies demonstrate activity of poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitors in isocitrate dehydrogenase (IDH) mutant gliomas. We investigated safety, tolerability, pharmacokinetics, and efficacy of the PARP inhibitor pamiparib in conjunction with metronomic low-dose temozolomide in patients with recurrent IDH mutant (IDHmt) gliomas in a multicenter Phase I/II/window of opportunity study.

methodsPatients received pamiparib in conjunction with daily temozolomide. Following Phase I determination of maximum tolerated dose (MTD), we enrolled 2 patient cohorts (Arm A, multiple prior chemotherapy regimens; Arm B, single prior regimen) in a 2-stage design. Exploratory cohorts examined grade 4 IDHmt patients and intratumoral pharmacokinetics of pamiparib. The primary endpoint was objective radiographic response (ORR) by RANO criteria.

resultsSixty-six subjects were enrolled. We established pamiparib 60 mg twice daily with temozolomide 20 mg daily as the phase II dose. In non-enhancing and enhancing tumor, pamiparib exhibited an unbound tumor/plasma ratio of 0.92 and 0.98, respectively. 0/15 Arm A and 1/24 Arm B patients achieved a centrally confirmed partial response. Median progression-free survival for Arm A was 5.9 months (95% CI, 1.2-14.8 months), and for Arm B was 9.7 months (95% CI, 5.7-21.7 months). Grade 3+ anemia and neutropenia affected 24% and 33% of patients, respectively. Twenty-two of 66 patients (33.3%) discontinued study treatment for reasons other than tumor progression.

conclusionsPamiparib appeared to achieve sufficient pharmacologically active concentrations in both enhancing and non-enhancing tumors. While some patients achieved prolonged progression-free survival, combination with temozolomide did not produce a meaningful ORR in IDHmt recurrent gliomas. Cumulative hematologic toxicity was substantial and impacted long-term tolerability.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsGliomaIsocitrate DehydrogenaseMutationNeoplasm Recurrence, LocalAdministration, MetronomicAdultAgedAntineoplastic Agents, AlkylatingFemaleFollow-Up StudiesHumansMaleMaximum Tolerated DoseMiddle AgedAntineoplastic Agents, AlkylatingIsocitrate DehydrogenaseTemozolomideclinical trialgliomaIDH mutationPARP inhibitorstemozolomide

Identifiers

PMID41099363
PMCPMC12979031

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.