{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T18:45:40Z","timestamp":1793817940251,"version":"4.6.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jiangsu Hengrui Medicine Co., Ltd"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biomark Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dalpiciclib (SHR6390) is a novel inhibitor of cyclin-dependent kinase 4\/6 which demonstrated promising anti-tumor potency in preclinical models. This first-in-human study was conducted to evaluate the tolerability, pharmacokinetics, safety, and preliminary antitumor activity of dalpiciclib in patients with advanced breast cancer (ABC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this open-label, phase 1 study, Chinese patients who had failed standard therapy were enrolled to receive oral dalpiciclib in 3\u2009+\u20093 dose-escalation pattern at doses of 25\u2013175\u2009mg. Eligible patients were given a single-dose of dalpiciclib in week 1, followed by once daily continuous doses for 3\u00a0weeks, and 1\u00a0week off in 28-day\u2009cycles. Based on the tolerability, pharmacokinetics, and activity data revealed from the dose-escalation phase, three dose cohorts were selected to expand to 8\u201310 patients. The primary endpoints were maximum tolerated dose (MTD) and pharmacokinetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between Apr 15, 2016 and Dec 21, 2018, 40 patients were enrolled; all were diagnosed of hormone receptor-positive and HER2-negative ABC. Dalpiciclib 100\u2009mg, 125\u2009mg, and 150\u2009mg cohorts were expanded to 10 patients. No dose-limiting toxicity was observed and the MTD was not reached. Adverse events (AEs) of grade 3 or 4 were observed in 22 (55.0%) of 40 patients, being neutropenia (52.5%), leukopenia (35.0%), thrombocytopenia (5.0%), and hypertension (2.5%). No serious AEs were reported. At the doses of 50\u2013175\u2009mg, steady state areas under the concentration-time curve and peak concentration increased almost proportionally with dose. The disease control rate (DCR) was 62.5% (25\/40, 95% CI: 45.8\u201377.3). Two patients (5%; 125\u2009mg and 150\u2009mg cohorts) achieved partial response, with responses lasting 169 and 356+ days, respectively. Among the three expansion cohorts, the 150\u2009mg cohort had the numerically highest DCR of 80.0% (95% CI: 44.4\u201397.5) and longest median progression-free survival of 8.4\u2009months (95% CI: 2.1\u2013not reached).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dalpiciclib showed acceptable safety profile and dose-dependent plasma exposure in Chinese patients with ABC. The recommended phase 2 dose was 150\u2009mg. Preliminary evidence of clinical activity was observed, which warrants further validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02684266\">NCT02684266<\/jats:ext-link>\n                      . Registered Feb 17, 2016.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40364-021-00271-2","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T12:03:34Z","timestamp":1618229014000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["A phase 1 study of dalpiciclib, a cyclin-dependent kinase 4\/6 inhibitor in Chinese patients with advanced breast cancer"],"prefix":"10.1186","volume":"9","author":[{"given":"Pin","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binghe","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Gui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenna","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"issue":"5","key":"271_CR1","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan D, Weinberg RA. 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The study protocol was approved (reference # 15\u2013140\/1067) by the ethics committee of the Cancer Hospital of the Chinese Academy of Medical Sciences (Beijing, China) and regulatory authorities. All patients provided written informed consent before enrollment.","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":"BX has received research funding from Jiangsu Hengrui Medicine, served as an advisor or consultant for Novartis and Roche and served on Speaker\u2019s Bureaus for AstraZeneca, Eisai, Pfizer and Roche. XZhang, GS, XZhu and JZ are employees of Jiangsu Hengrui Medicine. Other authors declared no conflict of interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"24"}}