{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:52:00Z","timestamp":1790805120927,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IMPACT Therapeutics Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Senaparib, a novel poly(ADP-ribose) polymerase 1\/2 inhibitor, demonstrated antitumor activity in preclinical studies. This phase I, first-in-human, dose-escalation\/-expansion study explored the pharmacokinetics, safety and tolerability, and preliminary antitumor activity of senaparib in Chinese patients with advanced solid tumors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and Methods<\/jats:title>\n                  <jats:p>Adults with advanced solid tumors who had failed \u00b31 line of prior systemic treatment were enrolled. Senaparib (once daily [QD]) dose was escalated from 2 mg until the maximum tolerated dose (MTD)\/recommended phase II dose (RP2D) using a modified 3 + 3 design. Dose expansion included: dose groups with \u22651 objective response and one dose higher, as well as those at the MTD\/RP2D. Primary objectives were to evaluate the safety and tolerability, and determine the MTD and\/or RP2D of senaparib.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Fifty-seven patients were enrolled across 10 dose groups (2-120 mg QD, and 50 mg twice daily). No dose-limiting toxicities were observed. The most common senaparib-related adverse events were anemia (80.9%), white blood cell count decreased (43.9%), platelet count decreased (28.1%), and asthenia (26.3%). Senaparib exposure increased dose proportionately at 2-80 mg; absorption saturated at 80-120 mg. Senaparib accumulation was minimal after repeated QD administration (accumulation ratio=1.1-1.5). The objective response rate was 22.7% (n=10\/44) overall (all partial responses) and 26.9% (n=7\/26) for patients harboring BRCA1\/BRCA2 mutations. Disease control rates were 63.6% and 73.1%, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Senaparib was well tolerated and demonstrated promising antitumor activity in Chinese patients with advanced solid tumors. The RP2D for this clinical study in China was identified as 100 mg QD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>ClinicalTrials.gov Identifier<\/jats:title>\n                  <jats:p>NCT03508011<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyad163","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T12:15:33Z","timestamp":1687263333000},"page":"e1259-e1267","source":"Crossref","is-referenced-by-count":9,"title":["Safety, Tolerability, and Pharmacokinetics of Senaparib, a Novel PARP1\/2 Inhibitor, in Chinese Patients With Advanced Solid Tumors: A Phase I Trial"],"prefix":"10.1093","volume":"28","author":[{"given":"Junning","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Fudan University Shanghai Cancer Center Shanghai , Shanghai , People\u2019s Republic of 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