TQB3617, a bromodomain and extra-terminal inhibitor, in patients with relapsed or refractory lymphoma: A multicenter, phase 1 trial.

BACKGROUND

Dysregulation of bromodomain and extra-terminal domain (BET) proteins causes aberrant acetylation of histones, triggering oncogene expression in malignancies. TQB3617 is an orally administered BET inhibitor that competitively binds to bromodomains and inhibits their activities.

METHODS

This phase 1 trial assessed the safety, pharmacokinetics, and efficacy of TQB3617 in patients with relapsed or refractory lymphomas. The primary endpoints were the safety, dose-limiting toxicity (DLT), and the recommended phase 2 dose (RP2D). Secondary endpoints included pharmacokinetics and efficacy. The trial is registered with ClinicalTrials.gov: NCT05110807.

FINDINGS: Using a 3+3 dose-escalation design, 39 patients were enrolled and treated with TQB3617 (0.05-0.25 mg) once daily. DLTs were reported in one patient at 0.1 mg with grade 3 herpes zoster and one patient at 0.25 mg with grade 3 thrombocytopenia and subcutaneous hemorrhage. The safety monitoring committee selected 0.1 mg once daily in two 21-day cycles followed by 14 days on and 7 days off in subsequent cycles as the RP2D. The most common grade 3-4 treatment-related adverse event (TRAE) was thrombocytopenia (14/39, 36%). Three patients discontinued study treatment due to TRAEs (all thrombocytopenia). The overall response rate (ORR) was 31% (12/39; complete response in 4 patients), with ORRs of 31% (5/16) in patients with Hodgkin's lymphoma, 31% (5/16) in patients with T cell lymphoma, and 29% (2/7) in patients with B cell lymphoma.

CONCLUSIONS

TQB3617 showed an acceptable safety profile and promising efficacy in patients with relapsed or refractory lymphomas.

FUNDING: This work was sponsored by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. and funded by the National Natural Science Foundation of China.