Purple Biotech has revealed positive new results from exploratory analyses conducted as part of a Phase I dose escalation study into CM24 plus nivolumab for advanced cancer.
The study enrolled 14 patients with advanced cancers including 11 patients with pancreatic adenocarcinoma (PDAC), two patients with colorectal adenocarcinoma (CRC) and one patient with papillary thyroid cancer.
The analyses conducted in eight evaluable PDAC patients demonstrate clinically meaningful and durable reductions in serum myeloperoxidase, a biomarker for neutrophil extracellular traps (NETs). This was seen immediately and 15 days after the first administration.
In addition, analyses of tumour samples derived from the evaluable PDAC patients suggest that patient survival may be positively associated with higher levels of CEACAM1+ tumour-infiltrating lymphocytes in the tumour microenvironment.
Preventing metastatic progression
NETs are web-like DNA structures and are covered with cancer-promoting proteins that are released by activated neutrophils and that have been shown to engulf tumours and promote immune evasion, tumour progression and metastases.
CM24, a first-in-class monoclonal antibody with the potential to treat multiple cancers, blocks CEACAM1, an immune checkpoint protein that supports tumour immune evasion and survival through multiple pathways.
When CEACAM1 is attached to NETs, it becomes a focal point of adhesion for cancer cells and, therefore, is suggested as a potential therapeutic target for preventing metastatic progression and immune evasion. In preclinical studies, CM24 has been shown to bind directly to NETs and to inhibit NET-induced cancer cell migration.
The company is evaluating CM24 in patients with metastatic pancreatic cancer (PDAC) in combination with the PD-1 inhibitor nivolumab and chemotherapy in a randomised Phase II study. The primary endpoint of this Phase II study is to evaluate preliminary efficacy through overall survival in second-line PDAC.
“These encouraging biomarker results provide initial evidence of certain mechanistically relevant biomarkers and may enable us to implement a biomarker-driven strategy that could identify patients who will benefit from CM24,” said Gil Efron, Chief Executive Officer, Purple Biotech. “We look forward to further data that may establish these findings in our ongoing randomised Phase II clinical study evaluating CM24 in combination with nivolumab and chemotherapy for treatment of PDAC.”