Comprehensive Analysis of the Investigational Anti-CCR8 Monoclonal Antibody: Cafelkibart (LM-108)

Executive Summary

Cafelkibart (LM-108) is an investigational, first-in-class, Fc-optimized humanized monoclonal antibody targeting the C-C motif chemokine receptor 8 (CCR8). Developed by LaNova Medicines Ltd. and now under the strategic stewardship of Sino Biopharmaceutical Ltd., LM-108 represents a novel immuno-oncology strategy designed to address a critical unmet need: resistance to immune checkpoint inhibitors (ICIs).[1] The core therapeutic thesis of LM-108 is predicated on its ability to selectively deplete tumor-infiltrating regulatory T cells (Tregs), a key immunosuppressive cell population within the tumor microenvironment (TME), thereby reactivating a potent anti-tumor immune response.[4]

Clinical development has yielded compelling efficacy signals in heavily pre-treated patient populations, particularly in cancers where ICIs have shown limited utility or where resistance has developed. In a pooled analysis of Phase 1/2 studies in patients with advanced gastric cancer, the majority of whom had failed prior anti-PD-1 therapy, LM-108 in combination with an anti-PD-1 antibody demonstrated an Objective Response Rate (ORR) of 36.1%.[7] This efficacy was profoundly enriched in a biomarker-selected subgroup of patients with high CCR8 expression who had progressed on first-line therapy, where an unprecedented ORR of 87.5% was observed.[7] Similarly, in advanced pancreatic cancer, the combination therapy achieved an ORR of 20.3% and a median Overall Survival (OS) of 10.02 months, with response rates rising to 33.3% in patients with high CCR8 expression.[4]