Merck KGaA, Darmstadt, Germany and Pfizer announced the opening of trial sites for an international phase III study of avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in patients with platinum-resistant/refractory ovarian cancer. The JAVELIN Ovarian 200 trial is the first phase III study of a PD-L1 inhibitor investigated as a treatment for platinum-resistant/refractory ovarian cancer.

The alliance also announced that the US Food and Drug Administration has provided approval to move forward with a phase III study of avelumab as a maintenance treatment, in the first-line setting, in patients with locally advanced or metastatic urothelial cancer. The first trial sites are expected to open shortly.

"There are limited treatment options for women with ovarian cancer, and the prognosis for women with platinum-resistant ovarian cancer is especially poor,” said Chris Boshoff, vice president and head of early development, translational and immuno-oncology at Pfizer Oncology.

"We have observed encouraging signs of early clinical activity of avelumab in patients with platinum-resistant or platinum-refractory ovarian cancer, and we hope to build on these results next year through a planned phase III study of avelumab in combination with platinum therapy in patients with previously untreated ovarian cancer.”

This phase III, randomized (1:1:1), open-label, parallel, multicenter, global study (JAVELIN Ovarian 200) is designed to evaluate the superiority of avelumab as a monotherapy or in combination with pegylated liposomal doxorubicin (PLD), compared with PLD alone, in treating patients with platinum-resistant/refractory ovarian cancer. The primary endpoint is overall survival (OS). Study investigators anticipate enrolling approximately 550 patients across more than 190 sites in Asia, Europe and North America.

Merck KGaA, Darmstadt, Germany, and Pfizer have also initiated a phase III study (JAVELIN Bladder 100) investigating avelumab as a maintenance treatment, in the first-line setting, in patients with locally advanced or metastatic urothelial cancer. This is currently the only phase III trial designed to evaluate an immunotherapy agent as a maintenance treatment, in the first-line setting, in patients with urothelial cancer.

“Locally advanced or metastatic urothelial cancer is another aggressive cancer, with the disease often progressing quickly following first-line treatment,” said Dr. Alise Reicin, head of global clinical development at Merck KGaA, Darmstadt, Germany’s biopharma business.

“It’s an exciting time for the Merck KGaA, Darmstadt, Germany, and Pfizer Alliance as we continue to accelerate our clinical development program, and now into urothelial cancer. This disease has an exceptionally high unmet need and we believe there is potential for our anti-PD-L1 antibody to be part of future treatment strategies.”

This open-label, multicenter, randomized, global, phase III study is designed to evaluate the safety and efficacy of avelumab plus best supportive care (BSC), compared with BSC alone, in patients with unresectable locally advanced or metastatic urothelial cancer whose disease did not progress on (or following) completion of first-line treatment with a platinum-containing chemotherapy. The primary endpoint of the study is OS, which will be assessed in two urothelial cancer patient populations: patients with PD-L1 positivity and all randomized patients.

JAVELIN Bladder 100 is expected to enroll 668 patients across more than 200 sites in 38 countries. PD-L1 expression status will be determined by retrospective analysis of mandatory tumour samples collected from patients enrolled in the trial. It is estimated that at least half of those patients randomized to treatment will be PD-L1-positive.

The clinical development programme for avelumab now includes more than 1,500 patients who have been treated across more than 15 tumour types, including breast cancer, gastric/gastro-esophageal junction cancers, head and neck cancer, melanoma, Merkel cell carcinoma, non-small cell lung cancer, ovarian cancer, renal cell carcinoma and urothelial (e.g. bladder) cancer. The alliance has initiated six pivotal trials, reaching its goal for 2015, with additional trials expected to initiate in 2016.

Avelumab is the proposed international non-proprietary 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.

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.

Urothelial cancer includes several tumors originating from the urothelial cells lining the bladder, renal pelvis and urethra. Bladder cancer accounts for 90 per cent of urothelial cancers,7 and is the ninth most common cancer globally. Approximately 400,000 new cases of bladder cancer are diagnosed and 150,000 deaths are attributed to this disease each year. The incidence and mortality of bladder cancer have remained unchanged over the past 25 years.