696P - SIM1811-03 (SIM0235), an anti-tumor necrosis factor receptor-2 (TNFR2) monoclonal antibody, in patients with advanced solid tumor and/or cutaneous T cell lymphomas (CTCL): Preliminary results from an on-going first-in-human phase I trial in China

Background

TNFR2 drives immune escape and tumor proliferation, and is highly expressed on tumor cells, immunosuppressive cells in the tumor microenvironment. SIM1811-03 is a humanized IgG1 monoclonal antibody that targets TNFR2,which demonstrated antitumor active in non-clinical models as single agent. SIM1811-03 is being evaluated in the First-in-Human study in patients with advanced solid tumors.

Methods

The study enrolled patients with advanced tumors who were not eligible for standard of care treatment. Patients received one dose of SIM1811-03 in cycle 0 and subsequently once every 2 weeks in dose from 0.5mg/mg to 25mg/mg. Based on emerging data a once every 3 weeks schedule in 40mg/kg dose was tested. The primary objectives were to determine the maximum-tolerated dose or recommended dose and to evaluate preliminary anti-tumor activity using either RECIST v1.1 for solid tumors. Secondary objectives were to assess safety and tolerability and to characterize pharmacokinetics and pharmacodynamics profiles.

Results

As of April 18, 2023, 22 patients received SIM1811-03 at doses of 0.5 mg/kg (n=3), 1.5 mg/kg (n=4), 5 mg/kg (n=4), 15 mg/kg (n=4), 25 mg/kg (n=4) Q2W and 40 mg/kg Q3W (n=3). No dose-limiting toxicity was observed and the MTD was not been reached. Majority of adverse events were Grade 1 or 2.There were two subjects with Grade 3/4 treatment-related adverse event. Two patients experienced treatment-related serious adverse event. SIM1811-03 showed a non-linear PK profile at the lower dose levels and a linear PK profile at the higher dose levels (15 to 40 mg/kg) with a half-life of about 12 days. TNFR2 receptor occupancy increased with SIM1811-03 concentration, and reached sustained saturation in peripheral blood CD14+ and CD16+ cells with the concentrations higher than about 10 ug/mL.

Conclusions

SIM1811-03 was well tolerated without DLTs reported across all dose levels and MTD was not reached. The preliminary PK and PD results support every 3-week dosing at 40mg/kg as the recommended dose for expansion. The clinical development of SIM1811-03 in combination with immunotherapy is planned.

Clinical trial identification

NCT05781386.

Editorial acknowledgement

Legal entity responsible for the study

Shandong Simcere Biopharmaceutical Co., Ltd.

Funding

Shandong Simcere Biopharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.