Merck KgaA and Pfizer announced the initiation of a phase III study, JAVELIN Ovarian 100, to evaluate the efficacy and safety of avelumab in combination with, and/or as follow-on (maintenance) treatment to, platinum-based chemotherapy in patients with locally advanced or metastatic disease (Stage III or Stage IV) with previously untreated epithelial ovarian cancer. JAVELIN Ovarian 100 is the first phase III study evaluating the addition of an immune checkpoint inhibitor to standard-of-care in first-line treatment for this aggressive disease.

“In an early ongoing study, avelumab showed encouraging tumor response rates in patients with recurrent or refractory ovarian cancer,” said Alise Reicin, M.D., Head of Global Clinical Development at the biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. “Historically, ovarian cancer presents as an advanced disease with poor survival rates. The hope is that avelumab can change the natural history of the disease and potentially take the survival rate beyond the current five year estimate.”

JAVELIN Ovarian 100 is an open-label, international, multi-center, randomized (1:1:1) phase III trial in treatment naïve patients with locally advanced or metastatic ovarian cancer (Stage III or Stage IV). This study is designed to evaluate the potential superiority of two first-line therapies with avelumab and platinum-based chemotherapy versus platinum-based chemotherapy alone, as assessed by progression-free survival. The study will enroll approximately 950 patients, who will receive concurrent avelumab and chemotherapy, avelumab following chemotherapy, or chemotherapy alone.

“Patients with ovarian cancer need additional treatment options. We believe there could be synergistic activity in the combination of avelumab and established treatments such as platinum-based chemotherapy,” said Chris Boshoff, M.D., Ph.D., head of Early Development, Translational and Immuno-Oncology, Oncology in Pfizer Global Product Development. “With two studies now underway of avelumab in ovarian cancer, we look forward to receiving the results from these trials and continuing to break ground in this hard-to-treat cancer.”

The alliance aims to build a strong foundation in ovarian cancer. In December 2015, Merck KgaA and Pfizer announced the initiation of an international phase III study of avelumab as a treatment for platinum-resistant/refractory ovarian cancer. As of May 2016, the complete JAVELIN clinical development program for avelumab includes approximately 2,200 patients enrolled, being treated across more than 15 tumor types.

Avelumab is the proposed nonproprietary name for the anti-PD-L1 monoclonal antibody (MSB0010718C). Avelumab is under clinical investigation and has not been proven to be safe and effective. There is no guarantee any product will be approved in the sought-after indication by any health authority worldwide.

Ovarian cancer causes more deaths than any other gynecologic cancer globally. Each year, nearly a quarter of a million women will be diagnosed with ovarian cancer worldwide. Women in Europe and Northern America have the highest incidence rates of ovarian cancer. Patients are said to have 'platinum-resistant' disease if the disease worsens within 6 months of completing platinum-based chemotherapy. One quarter of those who relapse after initial treatment, more than 4,300 women, will have platinum-resistant cancer, the most difficult-to-treat form of the disease.

Avelumab is an investigational, fully human anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1 interactions, avelumab is thought to enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to potentially 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-commercialize avelumab.