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3026 Background: TRS005 is a novel anti-CD20 antibody-drug conjugate targeting CD20 positive tumor cells to deliver MMAE into the cells via receptor-mediated endocytosis. The aim of this study was to evaluate the safety, pharmacokinetics, and anti-tumor activity of TRS005 in relapse/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). Methods: This first-in-human, single arm, multicenter, phase I, dose-escalation and expansion study conducted at 28 hospitals in China. The eligible patient had histologically confirmed CD20 positive B-cell lymphoma and had failed ≥2 prior lines of standard treatment. The dose-escalation phase involved 6 dose cohorts (from 0.1mg/kg to 2.1mg/kg) following a 3+3 design. Patients received TRS005 intravenously on day 1 of each 21-day cycle for 6 cycles. The dose cohort in which partial response (PR) or complete response (CR) was observed entered the dose-expansion phase. The safety, tolerability and efficacy of TRS005 were evaluated every two cycles. The primary endpoints were safety and pharmacokinetics. Secondary endpoints were objective response rate (ORR), disease control rate (DCR) and progression free survival (PFS) assisted by investigators. Results: From Aug 24 th ,2020 to Oct 23 th ,2023, 130 R/R B-cell NHL patients received treatment. The dose limiting toxicity was observed in the first patient in the 2.1mg/kg dose group during the dose-escalation phase. 70 patients had R/R diffuse large B cell lymphoma (DLBCL). Of the 70 R/R DLBCL patients, the median age was 59 (25-83) years, 82.9% of patients were in stage III-IV and 98.6% of patients received at least 2 lines of treatment (except one patient who only received 1 line of previous treatment). Overall, 88.6% of patients experienced all grades adverse events (AEs). Treatment-emergent adverse events (TEAEs) of ≥grade 3 occurred in 65.7% of patients, hematologic TEAEs were the most common. Two patients withdraw the treatment due to TEAEs and no TEAE related death were observed. At the data cutoff date of Nov 17 th , 2023, the median treatment duration was 4 (1-27) cycles. 58 patients were evaluated for efficacy and confirmed ORR was 46.6%, with a DCR of 75.9%. The highest ORR was seen in 1.8mg/kg dose cohort, with an ORR and DCR of 56.7% and 86.7%, respectively. The PFS was 5.6 (95% CI: 4.2-17.4) months and 12-month PFS was 35.1%. Conclusions: TRS005 is well-tolerated and exhibits encouraging anti-tumor efficacy in the treatment of R/R DLBCL. Clinical trial information: NCT05395533 . Table: see text
Shi et al. (Sat,) studied this question.