618O - A phase I study of TRS005: An anti-CD20-MMAE antibody-drug conjugate, in relapsed or refractory b cell non-Hodgkin lymphoma

Background

TRS005 is a newly developed anti-CD20-MMAE antibody-drug conjugate, targeting CD20+ tumor cells to deliver MMAE, a highly toxic antimitotic agent, into the cells via receptor-mediated endocytosis. Here we report the preliminary results of a phase I dose-escalation and expansion study which aimed to explore the safety, pharmacokinetics, and preliminary efficacy of TRS005 in CD20+ relapsed or refractory B-cell NHL (CTR20182204).

Methods

This was a single arm, multicenter, phase I study conducted at 11 centers in China. Eligible pts had histologically confirmed CD20-positive B-cell NHL and had failed ≥2 prior lines of standard treatment. The dose-escalation phase involved seven dose cohorts (0.1mg/kg, 0.5mg/kg, 1.0mg/kg, 1.5mg/kg, 1.8mg/kg, 2.1mg/kg, 2.3mg/kg) following a 3+3 design. Pts received TRS005 intravenously on day 1 of each 21-day cycle for 6 cycles. The dose cohort in which partial response or complete response was observed entered dose-expansion phase.

Results

From Aug 24, 2020 to Apr 29, 2022, 40 pts received treatment, including 14 pts in dose-escalation phase and 26 in dose expansion phase. The dose limiting toxicity was observed in first patient in the 2.1mg/kg cohort due to grade 3 drug-induced liver injury, and dose maximum tolerated dose was not reached by now. Overall, 78% of pts experienced treatment-related adverse events (TRAEs). TRAEs of ≥3 grade occurred in 34.1% of pts, with the most common being neutropenia (10.1%). At the data cutoff date on Apr 29, 2022, 35 pts were evaluable for efficacy and the confirmed objective response rate (ORR) was 37.1%, with a disease control rate (DCR) of 60%. ORR/DCR in different dose cohorts : 42.9% and 57.1% in 0.5mg/kg (n=7), 16.7% and 16.7% in 1.0mg/kg（n=6）, 43.8% and 68.8% in 1.5mg/kg, 50% and 100% in 1.8mg/kg (4 pts), 1 SD in 0.1mg/kg (1pt). ORR/DCR in different histology subtypes : 46.7% and 66.7% in DLBCL (n=15 ), 21.4% and 42.9% in FL (n=14), 100% and 100% in MCL(n=2), 50% and 100% in MZL (n=2).

Conclusions

TRS005 was well tolerated and showed promising efficacy in pts with relapsed or refractory B-cell NHL who failed standard second-line treatment.

Clinical trial identification

CTR20182204.

Editorial acknowledgement

Legal entity responsible for the study

Zhejiang Teruisi Pharmaceutical Inc.

Funding

Zhejiang Teruisi Pharmaceutical Inc.

Disclosure

All authors have declared no conflicts of interest.