Found 1 Presentation For Request "1537P"
1537P - Phase I/II study with CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer
- Niels Halama (Heidelberg, Germany)
NOX-A12 is a CXCL12 inhibitor that prevents activation of receptors CXCR4 and CXCR7 and blocks formation of CXCL12 concentration gradients. The Opera study is a phase I/II study to investigate pharmacodynamics of NOX-A12 monotherapy and safety and efficacy of a combination with pembrolizumab in metastatic MSS colorectal (CRC) and pancreatic (PaC) cancer where PD-1 inhibition alone has no clinical benefit.
Patients received NOX-A12 twice weekly for 2 weeks. Biopsies were taken from liver metastases before and after treatment to analyze immune cells and cytokines. Subsequently, patients received repeated 21-day cycles of NOX-A12 and pembrolizumab.
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.
Clinical trial identification
NCT03168139; EudraCT 2016-003657-15.
Legal entity responsible for the study
NOXXON Pharma AG.
NOXXON Pharma AG.
N. Halama, A. Williams, M. Suarez-Carmona, J. Schreiber, N. Hohmann, U. Pruefer, J. Krauss, D. Jaeger: Research grant/Funding (institution): NOXXON Pharma AG. A. Froemming, D. Beyer: Full/Part-time employment: NOXXON Pharma AG. J.U. Jungnelius, A. Mangasarian: Leadership role, Full/Part-time employment, Officer/Board of Directors: NOXXON Pharma AG.