Merck & Co. and Dynavax Technologies said today they will study cancer immunotherapy combinations of Dynavax’s toll-like receptor 9 (TLR9) agonist candidate SD-101 separately with two Merck drugs—the marketed Keytuda® (pembrolizumab), and investigational anti-interleukin-10 (anti-IL-10) immunomodulator MK-1966.

The value of the two clinical trial collaboration agreements was not disclosed.

The immunotherapies will be assessed in multiple studies expected to be launched in the second half of this year. The studies will be designed to evaluate the safety and efficacy of:

  • Combining SD-101 with Keytruda in patients with advanced melanoma, in a Phase Ib/II, multicenter, open-label trial.
  • Combining SD-101 with MK-1966 in patients with solid or hematological malignancies, in a Phase I trial.

“Our interest in working with Merck on these clinical collaborations was propelled by the synergistic activity we have seen when SD-101 is combined with checkpoint inhibitors in preclinical models,” Dynavax CEO Eddie Gray said in a statement.

Dynavax has agreed to sponsor and fund the SD-101 and Keytruda study, while Merck has agreed to sponsor and fund the SD-101 and MK-1966 study. The agreements include provisions allowing the companies to extend either collaboration to include a Phase III clinical trial.

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.

A second-generation, TLR9 agonist CpG-C class oligodeoxynucleotide, SD-101 is designed to activate multiple anti-tumor activities of innate immune cells, and activate plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. SD-101 is the subject of several Phase I/II oncology studies intended to assess its preliminary safety and activity.

MK-1966 is designed to block the activity of IL-10, which is known to down-modulate the immune activation required to kill tumor cells in the tumor microenvironment. Effects of down-modulation include decrease in cytokine production, upregulation of T regulatory cell activity and downregulation of antigen presenting cell activity. According to Merck, preclinical data has shown that co-administration of an anti-IL-10 with a TLR9 agonist may provide clinical benefit in treating some cancers.

Keytruda is a humanized monoclonal antibody that works by blocking interaction between PD-1 and its receptor ligands, PD-L1 and PD-L2—thus increasing the immune system’s ability to fight cancer in cells that produce the pigment responsible for color in the skin.

Keytruda—which won FDA approval in September 2014—is indicated for patients with unresectable or metastatic melanoma and disease progression following treatment with ipilimumab and, for patients who are BRAF V600 mutation positive, a BRAF inhibitor. Keytruda has been approved for intravenous infusion over 30 minutes every three weeks at a dose of 2 mg/kg.

According to Merck’s pipeline, last updated on the company’s website May 1, Keytruda is being investigated both as a monotherapy and in combination with other drugs in more than 100 clinical trials, across more than 30 tumor types and enrolling more than 16,000 patients.

Keytruda is under review in Europe for advanced (unresectable or metastatic) melanoma, as both first-line therapy and in previously treated patients. On May 22, Merck disclosed that the drug received a recommendation of approval for that indication from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency. The positive opinion was based on data from more than 1,500 patients with advanced melanoma treated with Keytruda as monotherapy in three studies.

Keytruda is also under clinical studies for additional indications that include gastric cancer (Phase II), bladder cancer (Phase III), head and neck cancer (Phase III), and non-small cell lung cancer (Phase III).








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