Merck KGaA, Darmstadt, Germany, Pfizer and Syndax Pharmaceuticals, Inc. have entered into a collaboration agreement to evaluate avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in combination with Syndax’s entinostat, an investigational oral small molecule that targets immune regulatory cells (myeloid-derived suppressor cells and regulatory T-cells), in patients with heavily pre-treated, recurrent ovarian cancer. Avelumab is currently under clinical investigation across a broad range of tumour types by the alliance between Merck KGaA, Darmstadt, Germany, and Pfizer.

This is an exclusive agreement between the alliance and Syndax to study the combination of these two investigational agents in ovarian cancer. Syndax will be responsible for conducting the phase Ib/II clinical trial in ovarian cancer.

“This collaboration with Syndax adds a new dimension to our quest to pursue combination immuno-oncology regimens based on compelling preclinical rationale and the potential to generate clinical results superior to those achieved with either agent alone,” said Dr. Mace Rothenberg, senior vice president of clinical development and medical affairs and chief medical officer for Pfizer Oncology.

“Combination therapy is the next frontier in immuno-oncology and a key strategy for the alliance,” said Dr. Luciano Rossetti, head of global research & development of the biopharma business of Merck KGaA, Darmstadt, Germany. “Avelumab as a monotherapy has already shown promising early activity in ovarian cancer in a Phase Ib trial, and through our ongoing research and this collaboration with Syndax, we will hopefully be able to make a real difference to women fighting this complex cancer.”

“We are delighted to be working with the alliance to explore the potential benefits of entinostat in combination with avelumab for ovarian cancer patients,” said Dr. Briggs W. Morrison, Syndax’s chief executive officer. “The continued interest from leading companies in investigating the potential of entinostat in combination with checkpoint inhibitors reflects positively on the potential mechanism of action of the molecule, and also reinforces our clinical strategy to explore entinostat for the benefit of patients across a broad range of solid tumour indications.”

Financial terms of the agreement were not disclosed.

Avelumab is the proposed international non-proprietary name for the anti-PD-L1 IgG1 monoclonal antibody (MSB0010718C). Avelumab is under clinical investigation. By inhibiting PD-L1 interactions, avelumab is thought to potentially enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialise avelumab.

Globally, ovarian cancer is the seventh most common cancer in women. Annually, nearly 239,000 cases are diagnosed worldwide. Ovarian cancer may be difficult to diagnose, as symptoms may appear only in the later stages, when the disease has spread beyond the ovaries. Outcomes for women with ovarian cancer are generally poor due to most patients presenting with advanced disease. The 5-year prevalence of women globally living with ovarian cancer is 22.6 per 100,000. Current treatment options for epithelial ovarian cancer may include surgery, radiotherapy, chemotherapy and targeted therapies. Women who are unable to undergo treatment with platinum-based chemotherapy, due to resistance or refractory disease, currently have very limited treatment options. Platinum-resistant ovarian cancer is defined as ovarian cancer that recurs within six months of completing primary chemotherapy with a platinum-based medication. Platinum-refractory ovarian cancer is defined as ovarian cancer that progresses during treatment with a platinum-based chemotherapy regimen. There is still a clear unmet need in ovarian cancer in relation to general disease awareness, improving initial investigations in primary and secondary care and novel therapies with demonstrable efficacy.