Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma

• Published in: Cancer medicine (Malden, MA) MA), 2024-07, Vol.13 (14), p.e7435-n/a
• Main Authors: Tang, Wenjiao, Li, Yan, Zhang, Li, Zhong, Xushu, Liang, Qiushi, Zheng, Yuhuan, Liu, Yuzhang, Wang, Yafei, Wang, Xunqiang, Zeng, Yun, Fang, Baijun, Zheng, Li, Niu, Ting
• Format: Article
• Language: English
• Subjects: Activities of daily living; Administration, Oral; Adult; Aged; antitumor activity; Clinical trials; Diarrhea; Dose-Response Relationship, Drug; Drug dosages; Drug Resistance, Neoplasm; Female; Humans; Kinases; Male; Maximum Tolerated Dose; Medical prognosis; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - pathology; Neoplasm Recurrence, Local - drug therapy; Neurotoxicity; Neutropenia; Peripheral neuropathy; Pharmacokinetics; Proteasome inhibitors; Proteasome Inhibitors - administration & dosage; Proteasome Inhibitors - adverse effects; Proteasome Inhibitors - pharmacokinetics; Proteasome Inhibitors - therapeutic use; Proteasomes; Proteins; relapsed and refractory multiple myeloma; Thrombocytopenia; Toxicity; Treatment Outcome; Urine
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.7435

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.