139P - Safety and clinical activity of a novel anti-CCR8 antibody (LM-108) as a single agent or in combination with pembrolizumab in patients with advanced solid tumors: Results of phase 1 study

Background

Tumor-infiltrating regulatory T cells (TITR) specifically demonstrate high expression of chemokine receptor 8 (CCR8). LM-108 is an anti-CCR8 monoclonal antibody that deplete TITR cells with enhanced antibody-dependent cell-mediated cytotoxicity. LM-108 alone or in combination with anti-PD-1 antibody has demonstrated excellent activity and safety profile in animal models. This phase 1/2 study (NCT05255484) evaluate LM-108 as single agent or in combination with pembrolizumab in patients with advanced solid tumor. Here, we present the results of phase 1 part.

Methods

This first-in-human, multicenter, open-label, phase 1/2 study enrolled patients aged ≥ 18 years with advanced solid tumors who had progressed on standard therapy, or were intolerable to the available standard therapy, or had no available standard therapy for treatment. For monotherapy, LM-108 were administered intravenously Q3W at dose levels of 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 20 mg/kg as per traditional 3+3 design. Combination therapy was evaluated at dose level of 10 mg/kg of LM-108 combined with 200 mg pembrolizumab Q3W.

Results

As of July 3, 2023, 24 patients (21 from monotherapy and 3 from combination therapy) were enrolled, no DLT was observed at all dose levels in monotherapy or combination therapy. MTD was not reached. The most frequent adverse events (AEs) related to the study drug were rash (8/24, Grade 1-2) and diarrhea (3/24, including 1 Grade 3). Out of 19 patients from monotherapy, 1 patient achieved partial response (PR) and 11 patients achieved stable disease (SD) with a disease control rate of 63%. One patient achieved PR and one patient achieved SD out of 2 evaluable patients from combination group. The two PR patients had duration of response over 6 months.

Conclusions

LM-108 monotherapy or in combination with pembrolizumab showed excellent safety profile and promising anti-tumor activity in patients with advanced solid tumors.

Legal entity responsible for the study

LaNova Medicines Limited.

Funding

LaNova Medicines Limited.

Disclosure

All authors have declared no conflicts of interest.