Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma
Abstract Objective TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first‐in‐human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM). Methods This is a multic...
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| Format: | Article |
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Wiley
2024-07-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.7435 |
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| _version_ | 1846115535795781632 |
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| author | Wenjiao Tang Yan Li Li Zhang Xushu Zhong Qiushi Liang Yuhuan Zheng Yuzhang Liu Yafei Wang Xunqiang Wang Yun Zeng Baijun Fang Li Zheng Ting Niu |
| author_facet | Wenjiao Tang Yan Li Li Zhang Xushu Zhong Qiushi Liang Yuhuan Zheng Yuzhang Liu Yafei Wang Xunqiang Wang Yun Zeng Baijun Fang Li Zheng Ting Niu |
| author_sort | Wenjiao Tang |
| collection | DOAJ |
| description | Abstract Objective TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first‐in‐human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM). Methods This is a multicenter phase I clinical trial consisting of the 3+3 dose‐escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28‐day cycle. Results Twenty‐five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose‐limiting 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 mg. Any‐grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time‐to‐plasma peak concentration of 0.8–1.5 h. The mean half‐life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response‐evaluable patients, 63.7% achieved stable disease or better. Conclusions TQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose‐expansion phase. |
| format | Article |
| id | doaj-art-79c01800aa18488eb3d8ccb5d79f76f4 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-79c01800aa18488eb3d8ccb5d79f76f42024-12-19T12:33:08ZengWileyCancer Medicine2045-76342024-07-011314n/an/a10.1002/cam4.7435Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myelomaWenjiao Tang0Yan Li1Li Zhang2Xushu Zhong3Qiushi Liang4Yuhuan Zheng5Yuzhang Liu6Yafei Wang7Xunqiang Wang8Yun Zeng9Baijun Fang10Li Zheng11Ting Niu12Department of Hematology, West China Hospital Sichuan University Chengdu ChinaDepartment of Hematology, West China Hospital Sichuan University Chengdu ChinaDepartment of Hematology, West China Hospital Sichuan University Chengdu ChinaDepartment of Hematology, West China Hospital Sichuan University Chengdu ChinaDepartment of Hematology, West China Hospital Sichuan University Chengdu ChinaDepartment of Hematology, West China Hospital Sichuan University Chengdu ChinaDepartment of Hematology Henan Cancer Hospital Zhengzhou ChinaChia Tai Tianqing Pharmaceutical Group Co., LTD. Nanjing Jiangsu ChinaChia Tai Tianqing Pharmaceutical Group Co., LTD. Nanjing Jiangsu ChinaDepartment of Hematology The First Affiliated Hospital of Kunming Medical University Kunming ChinaDepartment of Hematology Henan Cancer Hospital Zhengzhou ChinaDepartment of CTC Laboratory, West China Hospital Sichuan University Chengdu ChinaDepartment of Hematology, West China Hospital Sichuan University Chengdu ChinaAbstract Objective TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first‐in‐human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM). Methods This is a multicenter phase I clinical trial consisting of the 3+3 dose‐escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28‐day cycle. Results Twenty‐five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose‐limiting 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 mg. Any‐grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time‐to‐plasma peak concentration of 0.8–1.5 h. The mean half‐life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response‐evaluable patients, 63.7% achieved stable disease or better. Conclusions TQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose‐expansion phase.https://doi.org/10.1002/cam4.7435antitumor activitymaximum tolerated doseproteasome inhibitorsrelapsed and refractory multiple myeloma |
| spellingShingle | Wenjiao Tang Yan Li Li Zhang Xushu Zhong Qiushi Liang Yuhuan Zheng Yuzhang Liu Yafei Wang Xunqiang Wang Yun Zeng Baijun Fang Li Zheng Ting Niu Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma Cancer Medicine antitumor activity maximum tolerated dose proteasome inhibitors relapsed and refractory multiple myeloma |
| title | Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma |
| title_full | Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma |
| title_fullStr | Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma |
| title_full_unstemmed | Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma |
| title_short | Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma |
| title_sort | phase i study of tqb3602 an oral proteasome inhibitor in relapsed and refractory multiple myeloma |
| topic | antitumor activity maximum tolerated dose proteasome inhibitors relapsed and refractory multiple myeloma |
| url | https://doi.org/10.1002/cam4.7435 |
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