Evidence map›Paper›PMID 39917990›Full record

Trial reportCancer2025

Olaparib in treatment-refractory isocitrate dehydrogenase 1 (IDH1)- and IDH2-mutant cholangiocarcinoma: Safety and antitumor activity from the phase 2 National Cancer Institute 10129 trial.

Michael Cecchini, Mary Jo Pilat, Nataliya Uboha, Nilofer S Azad, May Cho, Elizabeth J Davis, Jordi Rodon Ahnert, Gabriel Tinoco, Geoffrey I Shapiro, Simon Khagi and 20 more

Abstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Circulating tumor DNA-based detection of molecular residual disease in isocitrate dehydrogenase-mutant cholangiocarcinoma for biomarker-guided therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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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

30 authors.

Michael CecchiniYale University School of Medicine, New Haven, Connecticut, USA.ORCID https://orcid.org/0000-0003-3504-0128
Mary Jo PilatKarmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
Nataliya UbohaUniversity of Wisconsin, Madison, Wisconsin, USA.
Nilofer S AzadJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
May ChoUniversity of California, Irvine, California, USA.
Elizabeth J DavisVanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA.ORCID https://orcid.org/0000-0001-7626-2435
Jordi Rodon AhnertMD Anderson Cancer Center, Houston, Texas, USA.
Gabriel TinocoThe Ohio State University, Columbus, Ohio, USA.
Geoffrey I ShapiroDana-Farber Cancer Institute, Boston, Massachusetts, USA.
Simon KhagiHoag Memorial Hospital Presbyterian, Newport Beach, California, USA.
Benjamin PowersUniversity of Kansas Cancer Center, Overland Park, Kansas, USA.
Kristen SpencerNew York University, New York, New York, USA.
Roman GroisbergRutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
Jan DrappatzUniversity of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Li ChenFrederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Biswajit DasFrederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Xun BaoKarmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
Jing LiKarmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
Azeet NarayanYale University School of Medicine, New Haven, Connecticut, USA.
Dennis VuYale University School of Medicine, New Haven, Connecticut, USA.
Abhijit PatelYale University School of Medicine, New Haven, Connecticut, USA.
Monica NigerMedical Oncology Department, Fondazione IRCCS Instituto Nazionale dei Tumori di Milano, Milan, Italy.
Deborah DoroshowTisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Diane DureckiYale University School of Medicine, New Haven, Connecticut, USA.ORCID https://orcid.org/0000-0002-6486-556X
Scott A BoernerYale University School of Medicine, New Haven, Connecticut, USA.
Ranjit BindraYale University School of Medicine, New Haven, Connecticut, USA.
Percy IvyCancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA.ORCID https://orcid.org/0000-0001-7747-072X
Derek ShyrDepartment of Biostatistics, Harvard University, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0002-2345-3390
Yu ShyrDepartment of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA.
Patricia M LoRussoYale University School of Medicine, New Haven, Connecticut, USA.

Funding

ViKTriY-PC Consortium Phase II SupplementUM1CA186689 · NCI · YALE UNIVERSITY · PI Patricia M. LoRusso · 2014 to 2026
$22.2M
The Johns Hopkins Translational Science Team for the ET-CTNUM1CA186691 · NCI · JOHNS HOPKINS UNIVERSITY · PI Jan Hendrik Beumer, Michael A Carducci · 2014 to 2026
$21.9M
NCI ET-CTN with Phase i Emphasis at UPCIUM1CA186690 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD, Farshid Dayyani · 2014 to 2026
$9.1M
Immunomodulatory Effects of Targeting DNA Repair with Novel Temozolomide Combinations in Colorectal CancerK08CA255465 · NCI · YALE UNIVERSITY · PI CECCHINI, MICHAEL · 2021 to 2025
$1.3M
Ben and Catherine Ivy FoundationNCI NIH HHS 1K08CA255465-01A1NCI NIH HHS K08 CA255465NCI NIH HHS NIH-1UM1CA186689NCI NIH HHS UM1 CA186689NCI NIH HHS UM1 CA186690NCI NIH HHS UM1 CA186691Rising Tide Foundation CCR-18-700
6 · The paper itself

Abstract

backgroundNeomorphic isocitrate dehydrogenase (IDH) mutations lead to the accumulation of 2-hydroxyglutarate (2-HG), an oncometabolite implicated in tumor progression via inhibitory effects on alpha-ketoglutarate. Moreover, mutant IDH-dependent accumulation of 2-HG results in homologous recombination deficiency (HRD), which preclinically renders tumors sensitive to poly(adenosine diphosphate ribose) polymerase inhibitors. Here, the results of the cholangiocarcinoma (CCA) arm of the National Cancer Institute (NCI) 10129 olaparib in IDH-mutant solid tumors basket trial are reported.

methodsOlaparib 300 mg twice daily was evaluated in an open-label, phase 2 clinical trial for treatment-refractory IDH-mutant solid tumors. Patients in the IDH-mutant CCA arm enrolled in two cohorts: (1) IDH inhibitor (IDHi) pretreated and (2) IDHi untreated, with a primary end point of overall response rate.

resultsNCI 10129 enrolled 30 patients with IDH-mutant CCA with no objective responses seen, and recruitment was closed early. Median progression-free survival (PFS) was 2.4 months (95% CI, 1.9 to 6.5 months) and median overall survival was 12.9 months (95% CI, 6.3 months to not reached). Eight patients (27%) had clinical benefit (CB), with a PFS of ≥6 months. Patients with CB had lower baseline 2-HG levels compared to those without CB (1.4 vs. 5.9 µmol/L; p = .01).

conclusionsOlaparib does not have sufficient single-agent activity to warrant further development in IDH-mutant CCA. However, a subgroup of patients demonstrated CB, and exploratory analysis revealed this subgroup to be enriched for lower baseline 2-HG levels. Future clinical trials leveraging the HRD properties of IDH mutations are warranted with enhanced patient selection and novel combination therapies.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaIsocitrate DehydrogenasePhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsAdultAgedAged, 80 and overDrug Resistance, NeoplasmFemaleHumansMaleMiddle AgedMutationNational Cancer Institute (U.S.)IDH1 protein, humanIDH2 protein, humanIsocitrate DehydrogenaseolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorscholangiocarcinomaDNA repairisocitrate dehydrogenase (IDH) mutationolaparibpoly(adenosine diphosphate ribose) polymerase (PARP) inhibitor

Identifiers

PMID39917990
PMCPMC11949439

What OpenQuestion holds

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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.