{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T11:29:22Z","timestamp":1793532562086,"version":"4.5.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Gateway for Cancer Research and Adult Brain Tumor Consortium","award":["UM1CA137443"],"award-info":[{"award-number":["UM1CA137443"]}],"id":[{"id":"https:\/\/ror.org\/04221f920","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Preclinical studies demonstrate activity of poly(adenosine 5\u2019-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixty-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pamiparib 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf246","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T11:54:46Z","timestamp":1760442886000},"page":"485-494","source":"Crossref","is-referenced-by-count":3,"title":["Phase I\/II and window-of-opportunity study of pamiparib and metronomic temozolomide for recurrent isocitrate dehydrogenase mutant gliomas"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1896-2502","authenticated-orcid":false,"given":"David","family":"Schiff","sequence":"first","affiliation":[{"name":"Division of Neuro-Oncology, University of Virginia School of Medicine , Charlottesville (D.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobu","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins School of Medicine , 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Detroit"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Campian","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine , St Louis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis B","family":"Nabors","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Alabama at Birmingham , Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byram H","family":"Ozer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine , Baltimore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arati","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University of Pennsylvania Perelman School of Medicine , Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-3664","authenticated-orcid":false,"given":"Antonio","family":"Omuro","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , New Haven"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Desideri","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins School of Medicine , Baltimore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraja","family":"Danda","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins School of Medicine , Baltimore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Grossman","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins School of Medicine , 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