CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with MSI-stable, metastatic CRC or pancreatic cancer

Abstract No : Abstract #1537P

Indication : Colorectal Cancer

Intervention : NOX-A12

Company : Noxxon Pharma

Technology : CXCL12 inhibitors


11 patients had CRC and 9 PaC. All patients were heavily pretreated with 5 (CRC) and 3 mean lines (PaC) of prior treatment. Best response to last prior treatment was progressive disease in 95% of cases. The AE profile was comparable with the pembrolizumab profile and typical for the underlying diseases. 2 weeks of NOX-A12 monotherapy induced changes in the tumor microenvironment: an upregulated cassette of Th1 cytokines in approx. 50% of patients, being associated with better clinical stabilization. Biopsy analysis before and after NOX-A12 monotherapy showed agglomeration of T cells and migration of T cells towards cancer cells in patients where NOX-A12 induced a Th1-type response. These trends suggest that CXCL12 inhibition increased effector immune cell infiltration of the tumor, resulting in a more effective immune response. 25% of patients achieved stable disease (SD) and long term disease control. Remarkably, 7 patients showed prolonged time on treatment vs. prior therapy. Median PFS was 1.87 months, OS was 42% at 6 and 22% at 12 months.


Agglomeration of T cells within tumors was seen in ∼half of the patients where NOX-A12 had induced a Th1-type cytokine response. This was accompanied by reduced distances between T and cancer cells, i.e. more engaged T cells. Increased infiltration of effector immune cells into tumor was associated with SD in 25% of patients and prolonged time on treatment vs. prior therapy for 35% of pts. Safety profile of the combination was consistent with that of pembrolizumab in advanced cancer patients.