Merck & Co. Inc. and Dynavax Technologies Corporation have entered into two clinical trial collaboration agreements to investigate the potential synergistic effect of combining immunotherapies from both companies' pipelines: Merck's anti-PD-1 therapy, Keytruda (pembrolizumab), and its investigational anti-interleukin-10 (anti-IL-10) immunomodulator, MK-1966, with Dynavax's investigational toll-like receptor 9 (TLR9) agonist, SD-101.

SD-101, KEYTRUDA, and MK-1966 are immunotherapies designed to enhance the body's own defenses in fighting cancer. SD-101 is designed to mediate anti-tumor effects by triggering both innate and adaptive immune responses, including the induction of high levels of Type 1 interferon to stimulate recruitment of T-cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 and PD-L2. MK-1966 is an investigational anti-IL-10 immunomodulator designed to neutralize the immune-suppressive environment for tumors.

The collaboration includes multiple studies that will evaluate the safety and efficacy of combining SD-101 with Keytruda in patients with advanced melanoma; this Phase I1b/II, multicenter, open-label study is expected to be initiated in the second half of 2015. Other studies will evaluate the safety and efficacy of combining SD-101 with MK-1966 in patients with solid or hematological malignancies; this Phase 1 study is expected to be initiated in the second half of 2015.

Under the agreement, Dynavax will sponsor and fund the SD-101 and Keytruda study. Merck will sponsor and fund the SD-101 and MK-1966 study. The agreements include provisions where the parties may agree to extend either collaboration to include a Phase III clinical trial. Additional details of the agreements between Dynavax and Merck, through a subsidiary, were not disclosed.

SD-101 is a proprietary, second-generation, TLR9 agonist CpG-C class oligodeoxynucleotide. SD-101 activates multiple anti-tumor activities of innate immune cells and activates plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. TLR9 agonists such as SD-101 enhance T and B cell responses and provide potent Type 1 interferon induction and maturation of plasmacytoid dendritic cells to antigen-presenting cells. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its preliminary safety and activity.

MK-1966, an investigational anti-interleukin-10 (anti-IL-10) immunomodulator, is designed to neutralize the immune-suppressive environment for tumors. MK-1966 blocks the activity of IL-10 which is known to down modulate the immune activation that is needed to kill tumor cells in the tumor microenvironment. These effects include decrease in cytokine production, upregulation of T regulatory cell activity and downregulation of antigen presenting cell activity. Based on preclinical data, co-administration of an anti-IL-10 with a TLR9 agonist may provide clinical benefit in the treatment of certain cancers.

Keytruda (pembrolizumab) is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. Keytruda is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Merck is advancing a broad and fast-growing clinical development program for Keytruda with more than 100 clinical trials across more than 30 tumor types and enrolling more than 16,000 patients,both as a monotherapy and in combination with other therapies.

Source: Merck & Co. Inc.