OREANDA-NEWS. June 02, 2015. Merck (NYSE:MRK), known as MSD outside the United States and Canada, and Dynavax Technologies Corporation (Nasdaq: DVAX) today announced they 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:

  • Safety and efficacy of combining SD-101 with KEYTRUDAin patients with advanced melanoma; this Phase 1b/2, multicenter, open-label study is expected to be initiated in the second half of 2015.
  • 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.

“The collaboration with Dynavax is rooted in Merck’s commitment to advancing breakthrough science in the field of immuno-oncology in order to address the complex interplay between the immune system and cancer,” said Dr. Eric Rubin, vice president and therapeutic area head, oncology early stage development, Merck Research Laboratories. “We are pleased that this latest collaboration not only investigates the potential of KEYTRUDA as a combination therapy, but also includes our new immunomodulator candidate, MK-1966.”

“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,” said Eddie Gray, chief executive officer of Dynavax. “These collaborations with Merck will facilitate our objective to demonstrate SD-101’s potential to complement multiple therapeutic modalities and thereby provide benefit to patients.”

Under the terms of 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 3 clinical trial. Additional details of the agreements between Dynavax and Merck, through a subsidiary, were not disclosed.

d on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or less. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

Based on its mechanism of action, KEYTRUDA may cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

For the treatment of advanced melanoma, KEYTRUDA was discontinued for adverse reactions in 6% of 89 patients who received the recommended dose of 2 mg/kg and 9% of 411 patients across all doses studied. Serious adverse reactions occurred in 36% of patients receiving KEYTRUDA. The most frequent serious adverse drug reactions reported in 2% or more of patients were renal failure, dyspnea, pneumonia, and cellulitis.

The most common adverse reactions (reported in ?20% of patients) were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%).

The recommended dose of KEYTRUDA is 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity. No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA. It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA. Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.