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 similar to 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 AUC(last) and C-max 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.