{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:37:45Z","timestamp":1790213865394,"version":"4.1.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T00:00:00Z","timestamp":1515369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T00:00:00Z","timestamp":1515369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n          <jats:p><jats:italic>Purpose<\/jats:italic> This phase 1 study examined safety, pharmacokinetics (PK), and efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor ABT-767 in patients with advanced solid tumors and <jats:italic>BRCA1\/2<\/jats:italic> mutations or with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. <jats:italic>Methods<\/jats:italic> Patients received ABT-767 monotherapy orally until disease progression or unacceptable toxicity. Dose was escalated from 20\u00a0mg once daily to 500\u00a0mg twice daily (BID). Dose-limiting toxicities, recommended phase 2 dose (RP2D), food effect, objective response rate, and biomarkers predicting response were determined. <jats:italic>Results<\/jats:italic> Ninety-three patients were treated with ABT-767; 80 had a primary diagnosis of ovarian cancer. ABT-767 demonstrated dose-proportional PK up to 500\u00a0mg BID and half-life of ~2\u00a0h. Food had no effect on ABT-767 bioavailability. Most common grade 3\/4 treatment-related adverse events were nausea, fatigue, decreased appetite, and anemia. Anemia showed dose-dependent increase. RP2D was 400\u00a0mg BID. Objective response rate by RECIST 1.1 was 21% (17\/80) in all evaluable patients and 20% (14\/71) in evaluable patients with ovarian cancer. Response rate by RECIST 1.1 and\/or CA-125 was 30% (24\/80) in patients with ovarian cancer. Mutations in <jats:italic>BRCA1 or BRCA2<\/jats:italic>, homologous recombination deficiency (HRD), and platinum sensitivity were associated with tumor response. Median progression-free survival was longer for HRD positive (6.7\u00a0months) versus HRD negative patients (1.8\u00a0months) with ovarian cancer. <jats:italic>Conclusions<\/jats:italic> ABT-767 had an acceptable safety profile up to the established RP2D of 400\u00a0mg BID and dose-proportional PK. Patients with <jats:italic>BRCA1 or BRCA2<\/jats:italic> mutation, HRD positivity, and platinum sensitivity were more sensitive to ABT-767.<\/jats:p>","DOI":"10.1007\/s10637-017-0551-z","type":"journal-article","created":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T04:45:55Z","timestamp":1515386755000},"page":"828-835","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A phase 1 study of PARP-inhibitor ABT-767 in advanced solid tumors with BRCA1\/2 mutations and high-grade serous ovarian, fallopian tube, or primary peritoneal cancer"],"prefix":"10.1007","volume":"36","author":[{"given":"Diane A. J.","family":"van der Biessen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jourik A.","family":"Gietema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja J. 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The study has been approved by the local ethics committees.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"DAJvdB, JAG, MJAdJ, IMED, MWdH, and CMLvH have no conflicts of interest to declare.KMT is a Myriad employee and may own Myriad stock. M Dudley, M Dunbar, RH, CS, HX, RKM, CKR, and PA are AbbVie employees and may own AbbVie stock. SPS was an AbbVie employee at time of study and may own AbbVie stock.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Patients provided written informed consent before participation in the trial.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}