{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:44:33Z","timestamp":1771047873297,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017239","name":"BeiGene","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017239","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pamiparib is a potent, selective, poly (ADP\u2010ribose) polymerase 1\/2 inhibitor that demonstrates synthetic lethality in cells with breast cancer susceptibility gene mutations or other homologous recombination deficiency. This two\u2010stage phase 1b study (NCT03150810) assessed pamiparib in combination with temozolomide (TMZ) in adult patients with histologically confirmed locally advanced and metastatic solid tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Oral pamiparib 60\u2009mg was administered twice daily. During the dose\u2010escalation stage, increasing doses of TMZ (40\u2013120\u2009mg once daily pulsed or 20\u201340\u2009mg once daily continuous) were administered to determine the recommended dose to be administered in the dose\u2010expansion stage. The primary objectives were to determine safety and tolerability, maximum tolerated\/administered dose, recommended phase 2 dose and schedule, and antitumor activity of pamiparib in combination with TMZ. Pharmacokinetics of pamiparib and TMZ and biomarkers were also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Across stages, 139 patients were treated (dose escalation, <jats:italic>n<\/jats:italic>\u2009=\u200966; dose expansion, <jats:italic>n<\/jats:italic>\u2009=\u200973). The maximum tolerated dose of TMZ, which was administered during dose expansion, was 7\u2010day pulsed 60\u2009mg once daily. The most common treatment\u2010emergent adverse events (TEAEs) were anemia (dose escalation, 56.1%; dose expansion, 63.0%), nausea (dose escalation, 54.5%; dose expansion, 49.3%), and fatigue (dose escalation, 48.5%; dose expansion, 47.9%). In the dose\u2010escalation stage, four patients experienced dose\u2010limiting toxicities (three neutropenia and one neutrophil count decreased). No TEAEs considered to be related to study drug treatment resulted in death. Antitumor activity was modest, indicated by confirmed overall response rate (dose escalation, 13.8%; dose expansion, 11.6%), median progression\u2010free survival (3.7 and 2.8\u2009months), and median overall survival (10.5 and 9.2\u2009months). Administration of combination therapy did not notably impact pamiparib or TMZ pharmacokinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pamiparib in combination with TMZ had a manageable safety profile. Further investigation of the efficacy of this combination in tumor types with specific DNA damage repair deficiencies is warranted.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.7385","type":"journal-article","created":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T05:49:36Z","timestamp":1720244976000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Phase 1b study to assess the safety, tolerability, and clinical activity of pamiparib in combination with temozolomide in patients with locally advanced or metastatic solid tumors"],"prefix":"10.1002","volume":"13","author":[{"given":"Agostina","family":"Stradella","sequence":"first","affiliation":[{"name":"Institut Catal\u00e0 d'Oncologia\u2013Hospital Duran I Reynals, L'Hospitalet de Llobregat  Catalunya Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Johnson","sequence":"additional","affiliation":[{"name":"Sarah Cannon 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UCL Cancer Institute, University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew D.","family":"Galsky","sequence":"additional","affiliation":[{"name":"The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emiliano","family":"Calvo","sequence":"additional","affiliation":[{"name":"START Madrid\u2010HM CIOCC, Centro Integral Oncol\u00f3gico Clara Campal, Hospital Universitario HM Sanchinarro, Calle O\u00f1a  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicente","family":"Baz","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen Macarena  Seville Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Moreno","sequence":"additional","affiliation":[{"name":"START Madrid\u2010FJD Fundacion Jimenez Diaz University Hospital  Madrid 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