{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:06:42Z","timestamp":1753862802883,"version":"3.41.2"},"reference-count":41,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Objective<\/jats:title><jats:p>TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the\u00a0first\u2010in\u2010human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed\/refractory multiple myeloma (RRMM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a multicenter phase I clinical trial consisting of the 3+3 dose\u2010escalation phase and dose expansion phase. Patients with MM who have received \u22652 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28\u2010day cycle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010five RRMM patients who relapsed or failed \u22652 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0\u2009mg dose group developed dose\u2010limiting toxicity events (one with grade 2 peripheral neuropathy [PN] complicated by pain and one with diarrhea and abdominal pain), leading to a maximum tolerated dose of 6.0\u2009mg. Any\u2010grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade \u22653 AEs occurred in 13 (52.0%). The most common grade \u22653 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade \u22653 PN occurred. TQB3602 was rapidly absorbed, resulting in a time\u2010to\u2010plasma peak concentration of 0.8\u20131.5\u2009h. The mean half\u2010life was approximately 82\u2009h. The AUC<jats:sub>last<\/jats:sub> and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> were approximately 1.9 times higher on day 15 than on day 1. Among 22 response\u2010evaluable patients, 63.7% achieved stable disease or better.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6\u2009mg and was adopted for an ongoing dose\u2010expansion phase.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.7435","type":"journal-article","created":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T03:45:17Z","timestamp":1721447117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase I study of <scp>TQB3602<\/scp>, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5576-1788","authenticated-orcid":false,"given":"Wenjiao","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Hematology, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5389-7550","authenticated-orcid":false,"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xushu","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Hematology, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiushi","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Hematology, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5855-4343","authenticated-orcid":false,"given":"Yuhuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Hematology, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology Henan Cancer Hospital  Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yafei","family":"Wang","sequence":"additional","affiliation":[{"name":"Chia Tai Tianqing Pharmaceutical Group Co., LTD.  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