Date: 2016-12-15
Type of information: Clinical research agreement
Compound: pembrolizumab and olaptesed pegol (NOX-A12)
Company: Noxxon Pharma (Germany) Merck&Co (USA - NJ)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: monoclonal antibody/immune checkpoint inhibitor. Keytruda® (pembrolizumab - MK-3475) is an investigational, highly selective monoclonal anti-PD-1 antibody designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system. Keytruda® is the first approved drug that blocks the PD-1 cellular pathway.
Olaptesed pegol/NOX-A12 specifically antagonizes CXCL12/SDF-1 (CXC Chemokine Ligand 12 / Stromal Cell-Derived Factor-1), a chemokine which attracts and activates immune and non-immune cells including stem cells from the bone marrow. CXCL12 binds with high affinity to two chemokine receptors, CXCR4 and CXCR7. The CXCL12 / CXCR4 / CXCR7 axis has been shown to play a role in stem cell mobilization, vasculogenesis, tumor growth and metastasis. CXCL12 signaling has been shown to play an important role in the pathophysiology of CLL, especially in the interaction of leukemic cells with the tissue microenvironment. The therapeutic concept of NOX-A12 is to inhibit such tumor-supporting interactions and thereby sensitize CLL cells to chemotherapy.
Disease: metastatic colorectal cancer, metastatic pancreatic cancer
Details:
- • On December 15, 2016, Noxxon Pharma announced the signature of a collaboration agreement with Merck & Co, under which the two companies will collaborate in a phase 1/2 clinical trial of Noxxon’s anti-CXCL12 agent, NOX-A12, and MSD’s anti-PD-1 inhibitor, Keytruda® (pembrolizumab), in patients with metastatic solid tumors that do not usually respond to checkpoint inhibitor monotherapy. The goal of the two-part, open-label phase 1/2 study is to evaluate pharmacodynamic effects and safety of NOX-A12 as a monotherapy in addition to safety and efficacy of NOX-A12 in combination with Keytruda® in patients with metastatic colorectal and pancreatic cancer. A total of twenty patients will be recruited, ten of each cancer type. Noxxon will be the sponsor of the study, which will be conducted in Europe.
- The design of the clinical trial was a collaborative effort between Noxxon and Merck & Co. Part 1 of the study, in which patients will receive NOX-A12 monotherapy for up to two weeks, will evaluate immune infiltrate changes within the tumor microenvironment induced by CXCL12 inhibition with NOX-A12 by comparing pre- and post-treatment biopsy specimens as well as the safety and tolerability of NOX-A12 in patients with metastatic (stage IV) colorectal and pancreatic cancer. Part 2 of the study, in which NOX-A12 is to be combined with Keytruda®, will assess the safety and tolerability of the combination in addition to the efficacy of treatment.
- NOX-A12, which inhibits the key tumor microenvironment chemokine CXCL12, may be a key partner for a wide range of IO (immuno-oncology) agents. Noxxon has generated promising pre-clinical and clinical data, including recent animal data showing synergy with a checkpoint inhibitor, as well as recent phase 2a trials in multiple myeloma and a second hematological cancer that showed a safety profile that supports further development and first signs of efficacy. Noxxon believes that its planned clinical study will position the drug to be combined with multiple classes of IO approaches including those acting on or through T cells and/or NK cells.
- Under the collaboration agreement, Merck & Co will provide Keytruda® to Noxxon for the conduct of the trial and has approved the trial design. Multiple paths for further development of the combination in pivotal clinical trials are envisioned in this agreement, although the agreement grants no commercial rights to either party for the other party’s compound. Additional details were not disclosed.
Financial terms:
Latest news: • On July 4, 2017, Noxxon Pharma announced that the first patients were treated in its Phase 1/2 clinical trial in patients with metastatic colorectal and pancreatic cancer at the National Center for Tumor Diseases in Heidelberg, Germany.
Is general: Yes
