1044P - A phase Ia first-in-human study of JS007, a novel anti-CTLA-4 monoclonal antibody, in patients with advanced solid tumors

Background

JS007 is a humanized IgG1 monoclonal antibody that targets cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) with superior binding affinity and anti-tumor activity from the preclinical study. Here we report the results of a first-in-human phase 1a study which assessed the safety, pharmacokinetics, and preliminary efficacy of JS007 in patients (pts) with advanced solid tumor (NCT05049265).

Methods

This open-label, single-arm, multicenter, phase 1a trial enrolled pts with advanced solid tumor who were resistant or intolerant to standard treatment, and included dose escalation and dose expansion phases. In the dose escalation phase, an accelerated titration followed by 3+3 design was used to assess the tolerability and safety of JS007 administered intravenously at doses of 0.03, 0.3, 1, 3 and 10 mg/kg Q3W. In the dose expansion phase, two dose cohorts were selected to enroll additional 6-9 pts per cohort.

Results

As of April 25, 2023, 26 pts had received JS007 (8 pts received > 3 prior lines of standard regimens, and 17 were pretreated with immunotherapy), including gastric adenocarcinoma (n=5) and non-small cell lung cancer pts (n=4). No dose-limiting toxicity was observed and the maximum tolerated dose was not reached. The dose cohorts of 3 and 10 mg/kg were expanded. Seventeen (65.4%) pts experienced treatment-related adverse events (TRAEs), with 8 (30.8%) experiencing grade 3 or higher TRAEs. The most common TRAEs (≥10%) were alanine aminotransferase increased (15.4%, 4/26), hemoglobin decreased (15.4%, 4/26), aspartate aminotransferase increased (11.5%, 3/26), and lipase increased (11.5%, 3/26). Among the evaluable 21 pts, one patient at 3 mg/kg achieved partial response and 11 reported disease stable (SD). One esophageal squamous cancer patient at 1 mg/kg showed SD for 8 months. Pharmacokinetics analysis showed serum exposure of JS007 generally increased with an increasing dose over the assessed dose range.

Conclusions

JS007 is well-tolerated with preliminary promising efficacy in heavily pretreated pts. The dose expansion phase is still ongoing, and the combination of JS007 with the anti-PD-1 antibody toripalimab is planned.

Clinical trial identification

NCT05049265.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Junshi Biosciences Co., Ltd.

Funding

Shanghai Junshi Biosciences Co., Ltd.

Disclosure

R. Zeng, S. Kuang: Personal, Full or part-time Employment: Shanghai Junshi Bioscience. All other authors have declared no conflicts of interest.