The University Medical Center (UMC) of the Johannes Gutenberg University Mainz is starting a new multi-center, Phase II clinical trial program evaluating DCVax®-L in combination with an anti–PD-1 monoclonal antibody (Pembrolizumab) for patients with liver metastases of primary colorectal carcinoma. The study aims to test the efficacy of dendritic cells (DC)-based therapy in combination with a checkpoint inhibitor antibody as a new approach to treat patients with synchronous or metachronous resectable liver metastases of colorectal carcinoma.

Colorectal cancer (CRC) is a major health burden, with a world-wide estimate of 1.4 million new cases annually. CRC is one of the most common causes of cancer-related death in the western world, resulting in approximately 700,000 deaths annually. Liver metastases are found in about 50% of all these patients. 

Combination of a therapeutic vaccine (such as DCVax^®-L) and a checkpoint inhibitor (such as Pembrolizumab) following resection of liver tumors is very promising to reactivate the immune system. The inherent logic of this combined approach is that the two treatments may be synergistic in mobilizing and sustaining a systemic immune response in these patients.

This Phase II trial involves a novel approach combining a broad spectrum, fully personalized vaccination strategy with a targeted immune system checkpoint inhibitor in colorectal carcinoma. The project enlarges the pipeline of clinical trials for multiple cancers and might further improve the repertoire of treatment options.

The Phase II trial program is a collaboration with Northwest Biotherapeutics (NASDAQ: NWBO) (“NW Bio”), a U.S. biotechnology company developing DCVax^®-L personalized immune therapies for solid tumor cancers, and the University Medical Center (UMC) of the Johannes Gutenberg University Mainz. MSD Sharp & Dohme GmbH, one of the leading global healthcare companies will provide the pembrolizumab for the study. (MSD Sharp & Dohme is the operating name used by USA based Merck & Co, Inc. outside the USA and Canada)

The University Medical Center at the Johannes Gutenberg University Mainz is a leading center of excellence in resection of colorectal cancer liver metastases. The 1^st Department of Medicine of the Medical Center of the Johannes Gutenberg University Mainz provides a wide range of treatments and conducts a variety of clinical trials, especially in the unit of gastrointestinal oncology.

After completing certain preparatory activities, including obtaining regulatory approvals, the Phase II trial will treat patients for up to 6 months with DCVax^®-L and the checkpoint inhibitor Pembrolizumab, followed by long-term follow-up. The effects of this combination therapy will be monitored with magnetic resonance imaging (MRI) as well as “liquid biopsy” measures.

DCVax^® is a platform technology that uses activated dendritic cells (DCs) and is designed to mobilize the immune system to attack cancer cells. DCs are the master cells of the immune system, and are responsible for presenting antigens (biomarkers) to induce a systemic immune response. Major advantages of DCVax^®-L include the mobilization of the entire immune system, the targeting of a full set of biomarkers on the patient’s tumor (to make it more difficult for the tumor to “escape”), the full personalization of the product to fit the patient’s own version of the tumors, and the multiplier effect of DCs mobilizing both large numbers and diverse populations of T cells. These factors are especially important in solid tumors because such tumors are so heterogeneous.

Pembrolizumab is a humanized and highly selective monoclonal immunoglobulin that blocks the interaction between the programmed cell death PD-1 cell surface receptor and its ligands, PD-L1 and PD-L2. Binding of these PD-1 ligands to the PD-1 receptor (found on T cells) inhibits T-cell proliferation and cytokine production. The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress immune control. Pembrolizumab binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, blocking PD-1 pathway-mediated inhibition of the anti-tumor immune response. Pembrolizumab (KEYTRUDA^®) has been approved by the European Medicines Agency as monotherapy for the treatment of advanced (unresectable or metastatic) melanoma in adults. Since July 2016, Pembrolizumab (KEYTRUDA^®) is also indicated for the treatment of locally advanced or metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumors express PD-L1 and who have received at least one prior chemotherapy regimen. Patients with EGFR and ALK positive tumor mutations should have received approved therapy for these mutations prior to receiving KEYTRUDA^®.

The trial will be conducted at about 10 sites in Germany, and UMC Mainz, Germany, will be the Sponsor. The study may also be expanded to other countries. MSD Sharp & Dohme GmbH supports the study by providing their novel checkpoint inhibitor Pembrolizumab. Close cooperation exists with Cognate BioServices and the Fraunhofer Institute for Cell Therapy and Immunology (IZI) Leipzig, Germany.

The IZKS is a professional academic clinical trial organization at the UMC Mainz. The IZKS connects clinical trial activities in clinical trial units with non-clinical and methodological study activities. Success and achievements have been judged as very good in several evaluations reflecting high level of quality and efficiency of tasks taken over in clinical trials by IZKS.

About Northwest Biotherapeutics

Northwest Biotherapeutics is a biotechnology company focused on developing personalized immunotherapy products designed to treat cancers more effectively than current treatments, without toxicities of the kind associated with chemotherapies, and on a cost-effective basis, in both the United States and Europe. The Company has a broad platform technology for DCVax dendritic cell-based vaccines. The Company’s lead program is a 348-patient Phase III trial in newly diagnosed Glioblastoma multiforme (GBM), which is on a partial clinical hold in regard to new screening of patients. GBM is the most aggressive and lethal form of brain cancer, and is an “orphan disease.” The Company is under way with a 60-patient Phase I/II trial with DCVax-Direct for all types of inoperable solid tumor cancers. It has completed the Phase I portion of the trial. The Company previously conducted a Phase I/II trial with DCVax^®-L for metastatic ovarian cancer together with the University of Pennsylvania. The Company previously received clearance from the FDA for a 612-patient Phase III trial in prostate cancer. In Germany, the Company has received approval of a 5-year Hospital Exemption for the treatment of all gliomas (primary brain cancers) outside the clinical trial.

About MSD Sharp & Dohme GmbH

MSD Sharp & Dohme GmbH is the German subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, a leading healthcare company that discovers, develops, manufactures and markets a wide range of innovative pharmaceutical products to improve human health and animal health. It focuses on several key therapeutic areas, including Cardiovascular, Diabetes, Immunology, Infectious Disease, Oncology and Women's Health. It also has a strong pipeline in oncology with Pembrolizumab (KEYTRUDA^®) being the most advanced pharmaceutical product.