Purple Biotech Initiates Phase II Trial of First-in-Class Anti-CEACAM1 Monoclonal Antibody CM24 in Second-Line Metastatic Pancreatic Cancer

On May 18, Purple Biotech announced the initiation of a Phase II clinical study for its anti-CEACAM1 monoclonal antibody CM24, evaluating the efficacy, safety, and tolerability of CM24 in combination with nivolumab and chemotherapy as a second-line treatment for metastatic pancreatic cancer.

CEACAM1, whose Chinese name is Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1, is an adhesion molecule that mediates cell adhesion. It promotes Fas-mediated apoptosis through interaction with β-catenin and enhances the cytotoxicity of natural killer cells against tumor cells. Currently, it has been found that high expression of CEACAM1 is associated with poor prognosis in various tumors because the signaling pathways of CEACAM1-CEACAM1 and CEACAM1-CEACAM5 can prevent tumor cell death by inhibiting the immune activity of TILs, reducing the phosphorylation of immune receptors, and lowering the phosphorylation levels of SHP1/2 in T cells and NK cells.

CM24 (humanized IgG4 monoclonal antibody) specifically binds to the extracellular domain of CEACAM1 with nanomolar affinity, blocking the interactions of CEACAM1-CEACAM1 and CEACAM1-CEACAM5 with CM24. It exerts anti-angiogenic effects, activates immune pathways, and promotes cytokine release, enhancing T cell and NK cell-mediated killing of tumor cells.

AACR2022 Conference Released Interim Data from the Phase Ib Study of CM24 in Combination with Opdivo. The results showed that the combination therapy had a good safety profile, with six grade 3 adverse events all unrelated to the drugs, and no grade 4 adverse events or deaths were found. Positive efficacy signals were observed in patients with advanced pancreatic cancer, with a disease control rate of 37% in eight patients and an objective response rate of 12%, including one confirmed partial response in a patient with metastatic pancreatic cancer. Additionally, three patients had stable disease, including two patients with pancreatic cancer and one patient with papillary thyroid carcinoma.

The launch of this Phase II study was jointly decided by Purple Biotech and Bristol-Myers Squibb. Based on positive interim data, both parties unanimously agreed to prioritize pancreatic cancer over lung cancer as the indication for development. Meanwhile, it was decided to expand the scale of enrolled participants and accelerate the trial progress, with the anticipated completion of the trial moved forward to within 2023.

Currently, CM24 is the only CEACAM1-targeted drug globally to have entered the clinical development stage.