{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T03:02:43Z","timestamp":1778036563955,"version":"3.51.4"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","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":[[2021,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:italic>Background<\/jats:italic>: Talazoparib is a poly(ADP-ribose) polymerase enzyme inhibitor. This open-label, non-randomized, phase 1 study of talazoparib investigated the safety, pharmacokinetics, and preliminary antitumor activity in Japanese patients with locally advanced or metastatic solid tumors, regardless of mutations in DNA damage repair-related genes, who are resistant to\/ineligible for standard therapies. <jats:italic>Methods<\/jats:italic>: Patients received talazoparib dosed orally at 0.75 or 1\u00a0mg once daily using a modified 3\u2009+\u20093 dose-escalation scheme. Primary endpoint was dose-limiting toxicities during the first cycle of talazoparib. <jats:italic>Results<\/jats:italic>: Nine patients (median age 62.0\u00a0years) were included: 3 and 6 patients at the 0.75 and 1.0\u00a0mg once-daily dose levels, respectively. No dose-limiting toxicities were reported. The most commonly reported treatment-emergent adverse events (\u22652 patients) were anemia, stomatitis, maculopapular rash, platelet count decreased, neutrophil count decreased, and alanine aminotransferase increased. Three patients had grade\u2009\u2265\u20093 treatment-emergent adverse events (anemia, brain metastases [1 patient each], and neutrophil and white blood cell count decreased [same patient]). Two patients temporarily discontinued treatment due to a treatment-emergent adverse event, and 1 patient required a dose reduction for neutrophil count decreased (all at 1\u00a0mg once daily). Talazoparib exposure (C<jats:sub>max<\/jats:sub> and AUC) after single and multiple dosing was slightly higher proportionally with talazoparib 1\u00a0mg than talazoparib 0.75\u00a0mg. The overall disease control rate was 44.4%, including 2 patients with stable disease. The recommended phase 2 dose of talazoparib was established as 1\u00a0mg once daily. <jats:italic>Conclusions<\/jats:italic>: Single-agent talazoparib was well tolerated and had preliminary antitumor activity in Japanese patients with advanced solid tumors. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> identifier: NCT03343054 (November 17, 2017).<\/jats:p>","DOI":"10.1007\/s10637-021-01120-7","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T05:02:44Z","timestamp":1624424564000},"page":"1568-1576","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Safety, pharmacokinetics, and preliminary efficacy of the PARP inhibitor talazoparib in Japanese patients with advanced solid tumors: phase 1 study"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8490-9064","authenticated-orcid":false,"given":"Yoichi","family":"Naito","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3675-953X","authenticated-orcid":false,"given":"Yasutoshi","family":"Kuboki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4050-2086","authenticated-orcid":false,"given":"Masafumi","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0833-3489","authenticated-orcid":false,"given":"Kenichi","family":"Harano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9203-4245","authenticated-orcid":false,"given":"Nobuaki","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-5263","authenticated-orcid":false,"given":"Shigeyuki","family":"Toyoizumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1919-2463","authenticated-orcid":false,"given":"Yuko","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4675-3975","authenticated-orcid":false,"given":"Natsuki","family":"Hori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1600-1062","authenticated-orcid":false,"given":"Takashi","family":"Nagasawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3730-6591","authenticated-orcid":false,"given":"Takahiro","family":"Kogawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"1120_CR1","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1177\/1758834011417039","volume":"3","author":"M Javle","year":"2011","unstructured":"Javle M, Curtin NJ (2011) The potential for poly (ADP-ribose) polymerase inhibitors in cancer therapy. 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All patients provided written informed consent prior to undergoing any study-specific procedure.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Yoichi Naito has received lecture fees, honoraria, or other fees from Pfizer, Novartis, and Chugai and research funds from Roche. Yasutoshi Kuboki has received lecture fees, honoraria, or other fees from Taiho Pharmaceutical and research funds from Taiho Pharmaceutical, Takeda Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Daichi-Sankyo, Boehringer Ingelheim, Incyte, Amgen KK, and Chugai Pharmaceutical. Masafumi Ikeda has received lecture fees, honoraria, or other fees from Novartis Pharma, Bayer, Eisai, Taiho Pharmaceutical, Eli Lilly Japan, and Chugai Pharmaceutical and research funds from Bayer, Yakult, ASLAN, Ono Pharmaceutical, Eisai, AstraZeneca, Chugai Pharmaceutical, Bristol Myers Squibb, Merck Serono, Novartis Pharma, Merck Sharp & Dome, and J-Pharma. Nobuaki Matsubara has received research funds from Pfizer Japan Inc. Shigeyuki Toyoizumi, Yuko Mori, Natsuki Hori, and Takashi Nagasawa are employees of Pfizer and report ownership interest in Pfizer.Kenichi Harano and Takahiro Kogawa have nothing to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}