Experimental Myeloma Agent Shows Promise in Combination with Immunotherapies

Inhibiting a key protein in the tumor microenvironment using Noxxon’s experimental agent NOX-A12 may enhance the clinical activity of immunotherapies that boost T-cells or natural killer cells, according to preclinical data presented at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen.

NOX-A12 (olaptesed pegol) is currently in Phase 2 clinical trials for multiple myeloma (NCT01521533) and relapsed chronic lymphocytic leukemia (NCT01486797) in combination with pre-existing drugs.

The poster presentation, titled “CXCL12 Inhibition with NOX-A12 (Olaptesed Pegol) Increases T and NK Cell Infiltration and Synergizes with Immune Checkpoint Blockade and ADCC in Tumour-Stroma Spheroids,” was shown at the conference by senior scientist Dirk Zboralski and hia colleagues, according to a press release.

Using its proprietary class of drugs called Spiegelmers, Noxxon aims to target the tumor microenvironment to enhance the effectiveness of cancer treatments including immuno-oncology therapies.

Spiegelmers are synthesized by mirroring a specific target molecule, identifying compounds that bind to the target, then synthesizing a mirror image of those compounds. Noxxon’s trademarked Spiegelmer platform has generated many assets, including NOX-A12.

NOX-A12 targets CXCL12, a key chemokine (signaling) protein that promotes tumor proliferation, new blood vessel formation, metastasis, and immune evasion. The agent has the ability to bind to two key sites on CXCL12, disrupting its activity and targeting it for degradation.

In preclinical and clinical studies, NOX-A12 has shown a synergistic effect when combined with a checkpoint inhibitor. The effect was also observed in recent Phase 2a clinical trials in multiple myeloma and chronic lymphocytic leukemia. Preliminary positive effectiveness and safety profiles support further development of the drug.

Given that CXCL12 is known to hinder the infiltration of tumor-killing immune cells into tumors, the new study tested whether NOX-A12 was able to enhance T-cell and NK (natural killer) cell infiltration into tumor-stroma spheroids, a preclinical model that mimics the complex tumor microenvironment.

Because the test worked, researchers believe the agent could be used in combination with drugs that enhance immune system activity.

More studies are needed to test the anti-tumor effectiveness of combining NOX-A12 with other immunotherapy agents.